cmd-1 encodes the single Caenorhabditis elegans calmodulin, a small EF-hand calcium sensor with four functional calcium-binding sites. The conserved core function is calcium-dependent binding and regulation of target proteins, including enzymes and spindle-associated factors. Experimental work in worms additionally places CMD-1 at spindle poles, centrosomes, the interphase nuclear membrane, and cell-cell boundaries in early embryos, and supports context-specific roles in meiotic spindle orientation, embryonic morphogenesis, apoptosis-related phenotypes, and neuronal chemotaxis. Falcon deep research further documents concrete downstream effector contexts: CMD-1 is the Ca2+/CaM activator component of the calcineurin phosphatase complex (with TAX-6 and CNB-1), it sets a transcriptionally controlled, limiting level of neuronal excitability, and it couples intestinal epithelial Ca2+ influx to NHX-6 activation in a gut-to-neuron host-defense pathway. Current GOA for cmd-1 contains no ISO annotations; the transfer-style annotations are IBA/IEA rather than ISO, so this ISO-focused pass mainly evaluates whether those orthology- derived calls are appropriately conservative.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005509
calcium ion binding
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: This phylogenetically inferred annotation matches the defining biochemical property of calmodulin family proteins. cmd-1 is the sole worm calmodulin, UniProt records four functional calcium-binding sites, and no conflicting evidence exists.
Reason: Calcium ion binding is a conserved and central calmodulin activity, so the orthology-based transfer is well supported and represents core function.
Supporting Evidence:
file:worm/cmd-1/cmd-1-uniprot.txt
This protein has four functional calcium-binding sites.
file:worm/cmd-1/cmd-1-deep-research-falcon.md
encoding the Ca2+-binding messenger protein **CMD-1**
|
|
GO:0005737
cytoplasm
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Cytoplasmic localization is consistent with cmd-1 being a broadly acting soluble calcium sensor. Experimental work in embryos also places CMD-1 on spindle/centrosomal structures and other non-nuclear sites, which is compatible with a general cytoplasmic annotation.
Reason: Cytoplasm is a correct high-level cellular location for calmodulin and is sufficiently general to retain as a core localization term.
Supporting Evidence:
file:worm/cmd-1/cmd-1-uniprot.txt
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
|
|
GO:0030234
enzyme regulator activity
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Calmodulin-Ca2+ complexes regulate multiple enzyme classes, including kinases and phosphatases, and UniProt explicitly describes cmd-1 as a mediator of enzyme control. The term is broad, but it captures a genuine conserved molecular role.
Reason: Although general, enzyme regulator activity is an appropriate conserved summary term for calmodulin and reflects core function rather than a lineage-specific phenotype. Falcon deep research identifies a concrete worm enzyme target: CMD-1 is the Ca2+/CaM activator subunit of the calcineurin phosphatase complex (TAX-6 catalytic, CNB-1 regulatory).
Supporting Evidence:
file:worm/cmd-1/cmd-1-uniprot.txt
Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+).
file:worm/cmd-1/cmd-1-deep-research-falcon.md
CMD-1 is part of the calcineurin activation complex (TAX-6/CNB-1/CMD-1)
|
|
GO:0000226
microtubule cytoskeleton organization
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: The transfer is plausible because worm experiments support CMD-1 roles in spindle organization and spindle orientation. However, the specific evidence is tied to cell-division contexts rather than to a universally defining calmodulin function.
Reason: Retain the annotation as valid but non-core because it reflects a real, experimentally supported spindle phenotype without being the central conserved biochemical identity of the gene. Falcon deep research confirms this is a recurring spindle-pole module function spanning multiple studies.
Supporting Evidence:
PMID:19219036
ASPM-1, together with calmodulin (CMD-1), promotes meiotic spindle organization
file:worm/cmd-1/cmd-1-deep-research-falcon.md
CMD-1 acts with ASPM-1/LIN-5 to recruit dynein and drive meiotic spindle rotation
|
|
GO:0005509
calcium ion binding
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: InterPro-derived calcium ion binding agrees with the IBA call and with the well-established EF-hand architecture of calmodulin.
Reason: This is a correct electronic annotation for a canonical EF-hand calcium- binding protein and matches core function.
Supporting Evidence:
file:worm/cmd-1/cmd-1-uniprot.txt
This protein has four functional calcium-binding sites.
|
|
GO:0072686
mitotic spindle
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: The ARBA localization is consistent with direct experimental embryo data showing CMD-1 accumulation on spindle structures. It is a correct but context-specific localization.
Reason: Mitotic spindle localization is supported, but it is not a universal core localization for calmodulin across all contexts.
Supporting Evidence:
file:worm/cmd-1/cmd-1-deep-research-falcon.md
CMD-1 acts with ASPM-1/LIN-5 to recruit dynein and drive meiotic spindle rotation
|
|
GO:0010629
negative regulation of gene expression
|
IMP
PMID:34499028 Neuronal calmodulin levels are controlled by CAMTA transcrip... |
MARK AS OVER ANNOTATED |
Summary: PMID:34499028 supports a specific autoregulatory loop in which high CMD-1 levels repress expression from the cmd-1 promoter through CAMT-1. That is more limited than generic negative regulation of gene expression.
Reason: The paper supports context-specific feedback on cmd-1 transcription, not a broad generic role in repressing gene expression across targets.
Supporting Evidence:
PMID:34499028
high levels of CMD-1 can repress expression from the cmd-1 promoter
|
|
GO:0050918
positive chemotaxis
|
IMP
PMID:34499028 Neuronal calmodulin levels are controlled by CAMTA transcrip... |
KEEP AS NON CORE |
Summary: Neuronal reduction of cmd-1 contributes to chemotaxis defects, and supplementing neuronal CMD-1 rescues attraction to several cues in the CAMT-1 regulatory context examined in the paper.
Reason: The phenotype is real but represents a specialized neuronal/behavioral context rather than the core conserved role of calmodulin. Falcon deep research underscores that neuronal CMD-1 abundance is a limiting, transcriptionally controlled determinant of sensory-neuron excitability and chemotaxis behavior.
Supporting Evidence:
PMID:34499028
restored normal chemotaxis toward salt, benzaldehyde, and diacetyl
file:worm/cmd-1/cmd-1-deep-research-falcon.md
reduced CaM levels are associated with hyperexcitable Ca2+ responses in sensory neurons
|
|
GO:0009792
embryo development ending in birth or egg hatching
|
IMP
PMID:14703012 Functional analysis of the single calmodulin gene in the nem... |
KEEP AS NON CORE |
Summary: cmd-1 RNAi causes severe embryonic lethality with disturbed morphogenesis, so the gene clearly contributes to successful embryogenesis.
Reason: This broad developmental phenotype is supported experimentally, but it is a pleiotropic consequence of depleting a global calcium sensor and should not be treated as core function. Falcon deep research quantifies the strong essentiality (~95% embryonic lethality by dsRNA injection) while framing it as downstream of CMD-1's global Ca2+-sensor role.
Supporting Evidence:
PMID:14703012
RNAi microinjection approach results in a severe embryonic lethal phenotype
file:worm/cmd-1/cmd-1-deep-research-falcon.md
cmd-1 knockdown produced **~95% embryonic lethality**
|
|
GO:0005813
centrosome
|
IDA
PMID:17716666 Cytokinesis is not controlled by calmodulin or myosin light ... |
KEEP AS NON CORE |
Summary: Full-text evidence from PMID:17716666 shows GFP-tagged CMD-1 accumulation at centrosomes in early embryos.
Reason: The localization is directly observed and valid, but it is a cell-division context rather than a core pan-context localization.
|
|
GO:0031965
nuclear membrane
|
IDA
PMID:17716666 Cytokinesis is not controlled by calmodulin or myosin light ... |
KEEP AS NON CORE |
Summary: The same embryo localization study reports CMD-1 at the interphase nuclear membrane.
Reason: The annotation is experimentally supported but context-specific and not a primary summary of calmodulin function.
|
|
GO:0071944
cell periphery
|
IDA
PMID:17716666 Cytokinesis is not controlled by calmodulin or myosin light ... |
KEEP AS NON CORE |
Summary: PMID:17716666 reports CMD-1 at the borders of abutting cells in embryos, which justifies a general cell periphery term.
Reason: Direct localization supports the term, but this is again a non-core, context-dependent localization.
|
|
GO:0072686
mitotic spindle
|
IDA
PMID:17716666 Cytokinesis is not controlled by calmodulin or myosin light ... |
KEEP AS NON CORE |
Summary: Direct imaging shows CMD-1 on spindle structures and not at the cleavage furrow in early embryos.
Reason: Correct experimental localization, but specialized to embryonic cell division rather than a core location.
|
|
GO:0005515
protein binding
|
IPI
PMID:19219036 NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote me... |
MODIFY |
Summary: PMID:19219036 places CMD-1 in an ASPM-1/LIN-5 spindle-pole complex, so a physical interaction claim is credible. However, protein binding is too generic for calmodulin and loses the informative calcium-dependent nature of its target interactions.
Reason: The interaction evidence should be retained, but the annotation should use a more informative calmodulin-appropriate term rather than generic protein binding.
Proposed replacements:
calcium-dependent protein binding
|
|
GO:0032880
regulation of protein localization
|
IMP
PMID:19219036 NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote me... |
KEEP AS NON CORE |
Summary: The meiosis study shows CMD-1 promotes accumulation of LIN-5 at meiotic and mitotic spindle poles, which is an experimentally grounded protein localization phenotype.
Reason: This process annotation is valid but reflects a specific spindle-pole context, not cmd-1's central conserved biochemical identity. Falcon deep research reinforces that the CMD-1/LIN-5/ASPM-1 module recruits dynein to spindle poles, and that this recruitment is gated by CDK-1.
Supporting Evidence:
PMID:19219036
promotes meiotic spindle organization and the accumulation of LIN-5 at meiotic and mitotic spindle poles
file:worm/cmd-1/cmd-1-deep-research-falcon.md
CDK-1 inhibits spindle rotation by blocking the interaction between the **CMD-1–LIN-5–ASPM-1** module and **DHC-1/dynein**
|
|
GO:0051296
establishment of meiotic spindle orientation
|
IMP
PMID:19219036 NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote me... |
KEEP AS NON CORE |
Summary: The paper directly concludes that LIN-5, ASPM-1, CMD-1 and dynein are required for spindle rotation during maternal meiosis.
Reason: Strong experimental support exists, but the process is specialized rather than core to calmodulin across contexts. Falcon deep research corroborates this with an independent follow-up study (Ellefson & McNally 2011) showing cmd-1(RNAi) abolishes meiosis I spindle rotation.
Supporting Evidence:
PMID:19219036
Spindle rotation during maternal meiosis is independent of GPR-1/2 and Galpha, yet requires LIN-5, ASPM-1, CMD-1 and dynein
file:worm/cmd-1/cmd-1-deep-research-falcon.md
cmd-1(RNAi) abolished meiosis I spindle rotation
|
|
GO:0051296
establishment of meiotic spindle orientation
|
IGI
PMID:19219036 NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote me... |
KEEP AS NON CORE |
Summary: The genetic interaction-based version of the same process annotation is consistent with the paper's functional dissection of the spindle-pole complex.
Reason: Retain as non-core for the same reason as the IMP entry: direct support, but specialized biology.
Supporting Evidence:
PMID:19219036
Spindle rotation during maternal meiosis is independent of GPR-1/2 and Galpha, yet requires LIN-5, ASPM-1, CMD-1 and dynein
|
|
GO:0016477
cell migration
|
IMP
PMID:14703012 Functional analysis of the single calmodulin gene in the nem... |
KEEP AS NON CORE |
Summary: cmd-1 RNAi embryos show aberrant cell migration patterns according to the abstract, supporting a migration-related phenotype.
Reason: This is a pleiotropic developmental phenotype observed after strong loss of a global calcium sensor, so it should be retained only as non-core.
Supporting Evidence:
PMID:14703012
Embryos show disturbed morphogenesis, aberrant cell migration patterns
|
|
GO:0042981
regulation of apoptotic process
|
IMP
PMID:14703012 Functional analysis of the single calmodulin gene in the nem... |
KEEP AS NON CORE |
Summary: The abstract reports multiple defects in apoptosis after cmd-1 depletion, which supports involvement in apoptosis-related regulation.
Reason: The phenotype is supported, but it is broad and likely pleiotropic rather than a core defining function of calmodulin.
Supporting Evidence:
PMID:14703012
multiple defects in apoptosis
|
|
GO:0043277
apoptotic cell clearance
|
IMP
PMID:14703012 Functional analysis of the single calmodulin gene in the nem... |
UNDECIDED |
Summary: The accessible abstract supports apoptosis defects, but it does not clearly distinguish cell corpse clearance/engulfment from upstream apoptosis defects.
Reason: This specific term may be correct, but the currently accessible evidence is insufficiently specific to review it confidently.
|
|
GO:0051726
regulation of cell cycle
|
IMP
PMID:14703012 Functional analysis of the single calmodulin gene in the nem... |
KEEP AS NON CORE |
Summary: Hyperproliferation in cmd-1 RNAi embryos is consistent with cell-cycle dysregulation after depletion of calmodulin.
Reason: The phenotype is experimentally supported, but it is a broad developmental consequence rather than a core molecular role.
Supporting Evidence:
PMID:14703012
a striking hyperproliferation of cells
|
Q: Which direct CMD-1 target proteins at spindle poles are most important for the meiotic spindle orientation phenotype in embryos?
Q: Which apoptosis and cell-migration phenotypes after cmd-1 depletion are direct CMD-1-dependent processes versus secondary consequences of broad calcium signaling collapse?
Q: Should calmodulin-family curation in nematodes explicitly add calcium-dependent protein binding where older annotations still use generic protein binding?
Experiment: Endogenous tagged CMD-1 affinity purification or proximity labeling under Ca2+-bound and Ca2+-free conditions to define direct embryo and neuronal target proteins.
Experiment: Rescue cmd-1 loss with EF-hand calcium-binding mutants to separate calcium sensing from possible scaffolding/localization roles at spindle poles.
Experiment: Tissue-specific depletion or rescue in embryos versus neurons to distinguish direct spindle and chemotaxis functions from pleiotropic systemic effects.
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The target gene symbol cmd-1 in C. elegans corresponds to the organism’s canonical calmodulin (CaM) gene, encoding the Ca2+-binding messenger protein CMD-1. Multiple independent C. elegans studies explicitly refer to cmd-1 as the single calmodulin gene and experimentally perturb cmd-1 to study CaM function in worms, matching the UniProt description provided (calmodulin family Ca2+ sensor with EF-hands). (karabinos2003functionalanalysisof pages 2-3, vuongbrender2021neuronalcalmodulinlevels pages 7-8)
Calmodulin (CaM) is a ubiquitous, highly conserved intracellular Ca2+ sensor that translates Ca2+ transients into downstream biochemical outputs by binding target proteins in a Ca2+-dependent manner, thereby modulating their activity, localization, or interactions. In C. elegans, CMD-1 abundance is limiting relative to its many targets, so changes in cmd-1 expression can strongly affect Ca2+-dependent physiology and behavior. (vuongbrender2021neuronalcalmodulinlevels pages 7-8)
In the worm nervous system, CMD-1 levels are directly coupled to neuronal excitability and stimulus-evoked Ca2+ dynamics: reduced CaM levels are associated with hyperexcitable Ca2+ responses in sensory neurons, while restoring CMD-1 levels can normalize neural activity and behavior. (vuongbrender2021neuronalcalmodulinlevels pages 6-7)
Functional depletion of CMD-1 by RNAi demonstrates that cmd-1 is essential for embryonic development. In dsRNA injection RNAi, cmd-1 knockdown produced ~95% embryonic lethality (progeny produced 28–45 h post-injection; n=177). (karabinos2003functionalanalysisof pages 2-3)
High-resolution 4-D lineage microscopy of cmd-1(RNAi) embryos revealed multiple cellular defects, including failed ventral closure, defective apoptotic cell engulfment, extra cleavages in E-derived intestinal precursor lineages, and cytokinesis failure in the D blastomere producing binucleate cells, consistent with CMD-1 acting broadly in Ca2+-dependent regulation of cell behaviors during early development. (karabinos2003functionalanalysisof pages 2-3)
A central mechanistic theme in C. elegans is that CMD-1 levels in neurons are tightly regulated and functionally critical. In camt-1 mutants (loss of the CAMTA-family transcription factor CAMT-1), CMD-1 mRNA levels are reduced ~2.5–4-fold across multiple neuron types (URX/AQR/PQR, BAG, AFD, RMG). (vuongbrender2021neuronalcalmodulinlevels pages 7-8, vuongbrender2021neuronalcalmodulinlevels pages 6-7)
Pan-neuronal supplementation of CMD-1 using a rab-3 promoter-driven cmd-1 transgene rescued multiple neuronal and behavioral defects (including O2-escape behavior, chemotaxis deficits, and sensory-neuron hyperexcitability in URX/BAG), establishing that CMD-1 is a functional determinant of circuit excitability. (vuongbrender2021neuronalcalmodulinlevels pages 7-8, vuongbrender2021neuronalcalmodulinlevels pages 6-7)
In oocyte meiosis/early embryos, CMD-1 participates in a spindle pole–associated module required for dynein-dependent meiotic spindle rotation. van der Voet et al. provide evidence that CMD-1 is part of a functional complex with ASPM-1 and LIN-5, and that cmd-1(RNAi) abolishes meiosis I spindle rotation. (voet2009numarelatedlin5aspm1 pages 1-5)
Mechanistically, Ellefson & McNally report that CDK-1 inhibits spindle rotation by blocking the interaction between the CMD-1–LIN-5–ASPM-1 module and DHC-1/dynein, and quantify dynein relocalization after CDK-1 inhibition (e.g., 14/21 embryos showing increased GFP::DHC-1 on poles/interpolar microtubules). (ellefson2011cdk1inhibitsmeiotic pages 6-8)
Expert curation of C. elegans phosphatase complexes documents CMD-1 (calmodulin) in a conserved calcineurin complex with the catalytic subunit TAX-6 and regulatory subunit CNB-1, consistent with canonical Ca2+/CaM-dependent activation of calcineurin. (bye‐a‐jee2020caenorhabditiselegansphosphatase pages 13-15)
A recent Nature Communications study describes a gut-to-neuron host-defense pathway in which pathogen-driven Ca2+ influx through GON-2 in intestinal epithelial cells activates CMD-1, which then activates the Na+/H+ exchanger NHX-6 to promote basolateral proton release; the protons activate ASIC-1 in cholinergic motor neurons to enhance cholinergic transmission and coordinate pathogen avoidance and intestinal immunity. (lei2026protonsignalinglinks pages 1-5)
CMD-1 functions as a hub Ca2+ sensor coupling Ca2+ dynamics to multiple downstream processes:
Tissue expression: A cmd-1 transcriptional reporter (8.9 kb upstream region fused to GFP) shows strong expression in neurons and muscle, including pharyngeal muscle, supporting broad physiological roles in excitable tissues and contractile systems. (vuongbrender2021neuronalcalmodulinlevels pages 8-10, vuongbrender2021neuronalcalmodulinlevels pages 7-8)
Regulatory localization context (neuronal control): CAMT-1 binds multiple cmd-1 upstream elements (~6.3 kb, 4.8 kb, 2.2 kb) and promotes cmd-1 expression in neurons; cmd-1 is also subject to negative feedback where increased CMD-1 can repress cmd-1 promoter activity in neurons via CAMT-1 IQ-domain-dependent mechanisms. (vuongbrender2021neuronalcalmodulinlevels pages 8-10, vuongbrender2020transcriptionalcontrolof pages 8-11)
Subcellular localization: The retrieved sources above provide strong tissue-level and functional-localization evidence (neurons, muscle, spindle poles via complex function), but do not directly quantify endogenous CMD-1 distribution among cytosol/nucleus/membranes in the text available here; therefore, subcellular localization beyond the functional contexts (e.g., spindle pole association through ASPM-1/LIN-5/dynein module) is not asserted further. (voet2009numarelatedlin5aspm1 pages 1-5, ellefson2011cdk1inhibitsmeiotic pages 6-8)
cmd-1 RNAi (loss-of-function):
* Embryonic lethality ~95% (dsRNA injection; n=177), and early embryonic arrest with morphogenesis/cytokinesis defects. (karabinos2003functionalanalysisof pages 2-3)
* Feeding RNAi yields weaker but measurable defects (8% embryonic lethality; 8% L1 arrest; 18% slow growth; reduced brood sizes among survivors). (karabinos2003functionalanalysisof pages 4-5)
Transcriptional downregulation of cmd-1 via CAMT-1 loss:
* cmd-1 mRNA reduced 2.5–4× in multiple neuron classes; behavioral and neuronal Ca2+ signaling defects are rescued by pan-neuronal cmd-1 supplementation. (vuongbrender2021neuronalcalmodulinlevels pages 7-8, vuongbrender2021neuronalcalmodulinlevels pages 6-7)
Humanized cmd-1 alleles (2023 development; disease-model application):
* Pathogenic calmodulin variant D96V in hcmd-1 background causes severe fitness defects with 93.5% fewer viable offspring, delayed reproduction (first offspring day 5–6 vs day 3–4), and strong rhythmic behavior defects including 40.5% reduced pharyngeal pumping; N54I reduces pumping by 10.8% and also affects defecation motor program frequency, whereas N98S does not affect pumping or DMP but impairs chemosensing. (jensen2023humancalmodulinmutations pages 4-5)
Meiotic spindle rotation defects:
* cmd-1(RNAi) abolishes meiosis I spindle rotation in the LIN-5/ASPM-1/dynein module context; CDK-1 inhibition rapidly increases dynein recruitment to poles via the CMD-1–LIN-5–ASPM-1 pathway. (voet2009numarelatedlin5aspm1 pages 1-5, ellefson2011cdk1inhibitsmeiotic pages 6-8)
A major recent development directly leveraging cmd-1 is the CRISPR “humanized” cmd-1 platform for modeling human calmodulin mutations in vivo. This work established measurable organism-level readouts (growth, fertility, pharynx pumping, defecation motor program, chemosensing) that discriminate effects of different CaM variants, providing a high-content functional annotation framework for CMD-1/CaM mutations and potentially for variant interpretation. (Publication date: March 2023; URL: https://doi.org/10.1093/hmg/ddad042) (jensen2023humancalmodulinmutations pages 4-5)
While not cmd-1-specific in the evidence available here, a 2024 eLife study strengthens the physiological importance of calcineurin signaling in C. elegans (a Ca2+/CaM-dependent phosphatase system for which CMD-1 is a core activator component), linking calcineurin inhibition to defecation motor program defects and lifespan extension mechanisms. This provides updated context for one major CMD-1-dependent signaling axis (CaM → calcineurin/TAX-6). (bye‐a‐jee2020caenorhabditiselegansphosphatase pages 13-15)
The following table compiles key experimental results, quantitative values, and references.
| Functional aspect | Evidence type & key experimental approach | Main finding (include quantitative values where available) | System/assay context (tissue/cell stage) | Primary citation (authors, year, journal) | DOI/URL | Evidence citation id (pqac-...) |
|---|---|---|---|---|---|---|
| Essential developmental function; embryonic viability; morphogenesis/cytokinesis/apoptosis | Loss-of-function by cmd-1 dsRNA microinjection and feeding RNAi; 4-D embryonic lineage microscopy | cmd-1 RNAi caused 95% embryonic lethality in progeny produced 28–45 h post-injection (n=177); rare survivors included 2% L1 arrest and 3% slow/uncoordinated animals. 4-D analysis of 9 embryos found arrest at the premorphogenetic stage with failed ventral closure, defective apoptotic cell engulfment, extra cleavages in E-lineage intestinal precursors, and failed cytokinesis of D blastomere producing binucleate cells. Feeding RNAi gave milder outcomes: 8% embryonic lethality, 8% L1 arrest, 18% slow growth; ~half of surviving adults laid only 1–20 embryos | Early embryo and postembryonic animals; whole-animal RNAi in C. elegans | Karabinos et al., 2003, European Journal of Cell Biology | https://doi.org/10.1078/0171-9335-00347 | (karabinos2003functionalanalysisof pages 2-3, karabinos2003functionalanalysisof pages 4-5) |
| Transcriptional regulation of neuronal CMD-1 by CAMT-1; neuronal rescue | FACS/RNA-seq of defined neuron types; ChIP-seq/ChIP pulldown; CRISPR promoter deletions; pan-neuronal rab-3p::cmd-1 rescue transgenes; behavioral and calcium-imaging assays | In camt-1 mutants, cmd-1/CaM mRNA was reduced 2.5- to 4-fold across multiple neuron types. CAMT-1 bound three promoter sites ~6.3 kb, 4.8 kb, and 2.2 kb upstream of cmd-1; deletion of all three sites (db1278) phenocopied camt-1 defects. Pan-neuronal CMD-1 expression rescued abnormal O2-escape, quiescence/locomotion, chemotaxis (salt, benzaldehyde, diacetyl), and neuronal hyperexcitability in URX/BAG; CMD-1 overexpression reduced cmd-1 promoter reporter output, supporting autoregulatory negative feedback via CAMT-1 | Nervous system; URX/AQR/PQR, BAG, AFD, RMG neurons; whole-animal behavior and calcium imaging | Vuong-Brender et al., 2021, eLife | https://doi.org/10.7554/eLife.68238 | (vuongbrender2021neuronalcalmodulinlevels pages 7-8, vuongbrender2021neuronalcalmodulinlevels pages 6-7, vuongbrender2021neuronalcalmodulinlevels pages 8-10) |
| Expression/localization pattern | Promoter-reporter transgene (8.9 kb cmd-1 upstream fused to GFP) | cmd-1p::gfp showed strong expression in neurons and muscle, including pharyngeal muscle; available evidence supports broad tissue expression but does not directly resolve subcellular localization of endogenous CMD-1 protein | Whole-animal reporter expression | Vuong-Brender et al., 2021, eLife | https://doi.org/10.7554/eLife.68238 | (vuongbrender2021neuronalcalmodulinlevels pages 8-10, vuongbrender2021neuronalcalmodulinlevels pages 7-8) |
| Meiotic spindle rotation complex with ASPM-1/LIN-5/dynein | RNAi phenotyping; live imaging; immunofluorescence; co-immunoprecipitation; LC-MS/MS; dynein localization assays | cmd-1 participates in a spindle-pole complex with ASPM-1 and LIN-5 that promotes dynein-dependent meiotic spindle rotation. cmd-1(RNAi) abolished meiosis I spindle rotation; ASPM-1/CMD-1 anchors LIN-5 at meiotic/mitotic spindle poles, enabling dynein recruitment. Follow-up work showed CDK-1 inhibits spindle rotation by blocking interaction of CMD-1–LIN-5–ASPM-1 with DHC-1/dynein; after CDK-1 inhibition, 14/21 embryos showed increased GFP::DHC-1 on poles/interpolar microtubules | Oocyte meiosis and early embryo spindle dynamics | van der Voet et al., 2009, Nature Cell Biology; Ellefson & McNally, 2011, Journal of Cell Biology | https://doi.org/10.1038/ncb1834; https://doi.org/10.1083/jcb.201104008 | (voet2009numarelatedlin5aspm1 pages 1-5, ellefson2011cdk1inhibitsmeiotic pages 6-8, voet2009numarelatedlin5aspm1 pages 5-7) |
| Calcineurin activation complex with TAX-6/CNB-1 | Expert curation of protein complex literature; complex annotation and mechanistic synthesis | CMD-1 is part of the calcineurin complex with catalytic subunit TAX-6 and regulatory subunit CNB-1; Ca2+-bound CMD-1 binds the calcineurin A subunit to promote full activation of the phosphatase complex. TAX-6 contains a CaM-binding region consistent with canonical Ca2+/CaM-dependent calcineurin regulation | Conserved Ca2+/calmodulin-dependent phosphatase signaling; multiple tissues/behaviors in C. elegans | Bye-A-Jee et al., 2020, The FEBS Journal | https://doi.org/10.1111/febs.15213 | (bye‐a‐jee2020caenorhabditiselegansphosphatase pages 13-15) |
| Humanized cmd-1 alleles as functional in vivo model of calmodulinopathy | CRISPR/Cas9 humanized hcmd-1 allele and pathogenic substitutions; fertility, growth, pharyngeal pumping, defecation motor program assays | Humanized hcmd-1 background enabled testing of pathogenic calmodulin variants. D96V had the strongest effect on Ca2+ binding and caused severe growth/fertility defects with 93.5% fewer viable offspring than hcmd-1 controls; first offspring typically on day 5–6 vs day 3–4 in controls/other strains. Pharynx pumping fell by 10.8% for N54I and 40.5% for D96V; N54I and D96V also reduced defecation motor program cycle frequency, whereas N98S had little effect on rhythmic behaviors but impaired chemosensing | Whole-animal physiology; pharynx, enteric/body-wall muscle, germline | Jensen et al., 2023, Human Molecular Genetics | https://doi.org/10.1093/hmg/ddad042 | (jensen2023humancalmodulinmutations pages 4-5) |
| Intestinal epithelial signaling; activation of NHX-6 in host defense pathway | Functional pathway dissection linking Ca2+ influx, CMD-1, NHX-6, proton release, and neuronal ASIC-1 signaling | Pathogen-stimulated Ca2+ influx through GON-2 in intestinal epithelial cells activates CMD-1, which activates NHX-6 to drive basolateral proton release. These protons stimulate ASIC-1 in cholinergic motor neurons to promote pathogen avoidance and intestinal innate immunity; mouse NHE1 and ASIC1a could substitute for nematode proteins, supporting pathway conservation | Intestinal epithelial cells to cholinergic neurons; host-defense signaling | Lei et al., 2026, Nature Communications | https://doi.org/10.1038/s41467-026-71088-6 | (lei2026protonsignalinglinks pages 1-5) |
Table: This table summarizes the main experimental findings supporting functional annotation of C. elegans CMD-1/calmodulin, including essential developmental roles, neuronal regulation, spindle functions, calcineurin signaling, disease-model alleles, and intestinal defense signaling. It highlights assay types, quantitative findings, and citation IDs for rapid traceability.
References
(karabinos2003functionalanalysisof pages 2-3): Anton Karabinos, Ingo Büssing, Ekkehard Schulze, Jian Wang, Klaus Weber, and Ralf Schnabel. Functional analysis of the single calmodulin gene in the nematode caenorhabditis elegans by rna interference and 4-d microscopy. European journal of cell biology, 82 11:557-63, Nov 2003. URL: https://doi.org/10.1078/0171-9335-00347, doi:10.1078/0171-9335-00347. This article has 23 citations and is from a peer-reviewed journal.
(vuongbrender2021neuronalcalmodulinlevels pages 7-8): Thanh Thi Vuong-Brender, Sean Flynn, Yvonne Vallis, Saliha E Sönmez, and Mario de Bono. Neuronal calmodulin levels are controlled by camta transcription factors. eLife, Sep 2021. URL: https://doi.org/10.7554/elife.68238, doi:10.7554/elife.68238. This article has 11 citations and is from a domain leading peer-reviewed journal.
(vuongbrender2021neuronalcalmodulinlevels pages 6-7): Thanh Thi Vuong-Brender, Sean Flynn, Yvonne Vallis, Saliha E Sönmez, and Mario de Bono. Neuronal calmodulin levels are controlled by camta transcription factors. eLife, Sep 2021. URL: https://doi.org/10.7554/elife.68238, doi:10.7554/elife.68238. This article has 11 citations and is from a domain leading peer-reviewed journal.
(voet2009numarelatedlin5aspm1 pages 1-5): Monique van der Voet, Christian W. H. Berends, Audrey Perreault, Tu Nguyen-Ngoc, Pierre Gönczy, Marc Vidal, Mike Boxem, and Sander van den Heuvel. Numa-related lin-5, aspm-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical lin-5/gpr/gα. Nature Cell Biology, 11:269-277, Feb 2009. URL: https://doi.org/10.1038/ncb1834, doi:10.1038/ncb1834. This article has 157 citations and is from a highest quality peer-reviewed journal.
(ellefson2011cdk1inhibitsmeiotic pages 6-8): Marina L. Ellefson and Francis J. McNally. Cdk-1 inhibits meiotic spindle shortening and dynein-dependent spindle rotation in c. elegans. The Journal of Cell Biology, 193:1229-1244, Jun 2011. URL: https://doi.org/10.1083/jcb.201104008, doi:10.1083/jcb.201104008. This article has 45 citations.
(bye‐a‐jee2020caenorhabditiselegansphosphatase pages 13-15): Hema Bye‐A‐Jee, Rossana Zaru, Michele Magrane, and Sandra Orchard. caenorhabditis elegans phosphatase complexes in uniprotkb and complex portal. The FEBS Journal, 287:2664-2684, Feb 2020. URL: https://doi.org/10.1111/febs.15213, doi:10.1111/febs.15213. This article has 8 citations.
(lei2026protonsignalinglinks pages 1-5): Ying Lei, Xueliang Zhan, Chao Chen, Yuxin Liu, Ying Wang, and Ping Liu. Proton signaling links epithelial sensing to neural control of host defense in c. elegans. Nature Communications, Mar 2026. URL: https://doi.org/10.1038/s41467-026-71088-6, doi:10.1038/s41467-026-71088-6. This article has 0 citations and is from a highest quality peer-reviewed journal.
(vuongbrender2021neuronalcalmodulinlevels pages 8-10): Thanh Thi Vuong-Brender, Sean Flynn, Yvonne Vallis, Saliha E Sönmez, and Mario de Bono. Neuronal calmodulin levels are controlled by camta transcription factors. eLife, Sep 2021. URL: https://doi.org/10.7554/elife.68238, doi:10.7554/elife.68238. This article has 11 citations and is from a domain leading peer-reviewed journal.
(vuongbrender2020transcriptionalcontrolof pages 8-11): Thanh T. K. Vuong-Brender, Sean M. Flynn, and Mario de Bono. Transcriptional control of calmodulin by camta regulates neural excitability. bioRxiv, Sep 2020. URL: https://doi.org/10.1101/2020.09.14.296137, doi:10.1101/2020.09.14.296137. This article has 1 citations.
(karabinos2003functionalanalysisof pages 4-5): Anton Karabinos, Ingo Büssing, Ekkehard Schulze, Jian Wang, Klaus Weber, and Ralf Schnabel. Functional analysis of the single calmodulin gene in the nematode caenorhabditis elegans by rna interference and 4-d microscopy. European journal of cell biology, 82 11:557-63, Nov 2003. URL: https://doi.org/10.1078/0171-9335-00347, doi:10.1078/0171-9335-00347. This article has 23 citations and is from a peer-reviewed journal.
(jensen2023humancalmodulinmutations pages 4-5): Helene H Jensen, Magnus T Frantzen, Jonas L Wesseltoft, Ana-Octavia Busuioc, Katrine V Møller, Malene Brohus, Palle R Duun, Mette Nyegaard, Michael T Overgaard, and Anders Olsen. Human calmodulin mutations cause arrhythmia and affect neuronal function in c. elegans. Human Molecular Genetics, 32:2068-2083, Mar 2023. URL: https://doi.org/10.1093/hmg/ddad042, doi:10.1093/hmg/ddad042. This article has 20 citations and is from a domain leading peer-reviewed journal.
(voet2009numarelatedlin5aspm1 pages 5-7): Monique van der Voet, Christian W. H. Berends, Audrey Perreault, Tu Nguyen-Ngoc, Pierre Gönczy, Marc Vidal, Mike Boxem, and Sander van den Heuvel. Numa-related lin-5, aspm-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical lin-5/gpr/gα. Nature Cell Biology, 11:269-277, Feb 2009. URL: https://doi.org/10.1038/ncb1834, doi:10.1038/ncb1834. This article has 157 citations and is from a highest quality peer-reviewed journal.
just fetch-gene worm cmd-1: 21 annotations total. There are no current ISO evidence-code annotations for cmd-1; the transfer-style set is IBA plus IEA, so the ISO-focused review mainly evaluates whether those orthology/electronic calls are conservative enough.cmd-1 is the single C. elegans calmodulin. UniProt describes it as a 149 aa calmodulin with four functional calcium-binding sites and broad Ca2+-dependent regulation of enzymes, ion channels, and other proteins [PMID:17854888 Ca(2+)/Calmodulin-binding proteins from the C. elegans proteome., "Calmodulin (CaM) is the primary Ca(2+)-sensor that regulates a wide variety of cellular processes in eukaryotes."].cmd-1 knockdown caused embryonic lethality, disturbed morphogenesis, aberrant cell migration, hyperproliferation, and apoptosis defects [PMID:14703012 Functional analysis of the single calmodulin gene in the nematode Caenorhabditis elegans by RNA interference and 4-D microscopy., "Embryos show disturbed morphogenesis, aberrant cell migration patterns, a striking hyperproliferation of cells and multiple defects in apoptosis."].calcium ion binding, cytoplasm, and enzyme regulator activity as core.IBA microtubule organization term as plausible but non-core rather than as a defining calmodulin function.protein binding is too generic for calmodulin; preferred replacement is GO:0048306 calcium-dependent protein binding.negative regulation of gene expression is over-annotated relative to the specific cmd-1 autoregulatory feedback described in PMID:34499028.apoptotic cell clearance remains the weakest call because the accessible abstract for PMID:14703012 supports apoptosis defects generally, but not clearly corpse clearance specifically.Exported on March 22, 2026 at 01:20 AM
Organism: Caenorhabditis elegans
Sequence:
MADQLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVTMMTTK
I begin by dissecting the InterPro architecture. The sequence is dominated by calcium-sensing EF-hand modules: IPR011992 (EF-hand domain pair, residues 2–147) indicates two paired helix–loop–helix units that coordinate Ca2+ and undergo concerted conformational switching. This is reinforced by IPR002048 (EF-hand domain, residues 8–149), which maps nearly the entire polypeptide to canonical EF-hand folds, and by IPR018247 (EF-Hand 1, calcium-binding site, residues 21–142), which flags multiple Ca2+-ligating loops distributed through the core. The family-level assignment IPR050230 (Calmodulin/Myosin light chain/Troponin C-like, residues 2–148) situates the protein within the classical Ca2+-sensor clade that transduces Ca2+ binding into protein–protein interaction events rather than enzymatic catalysis. The architecture—an EF-hand pair spanning essentially the full length—is characteristic of calmodulin-like sensors that switch between apo and Ca2+-bound states to regulate diverse targets.
This EF-hand array dictates molecular function. The repeated EF-hands and their cooperative binding loops cause high-affinity calcium ion binding, which in turn exposes hydrophobic target-recognition surfaces that drive Ca2+-dependent regulatory interactions. This mechanistic logic directly supports GO:0005509 calcium ion binding as the core molecular function.
From this Ca2+-responsive binding mechanism, I infer the biological process. EF-hand sensor systems act as hubs that decode transient Ca2+ spikes and propagate signals to enzymes, channels, and cytoskeletal assemblies. Such coupling of Ca2+ sensing to effector regulation is the defining currency of intracellular signaling cascades. Therefore, the EF-hand-driven switching behavior compels a role in calcium-mediated signaling, aligning with the concept formalized as GO:0019722 calcium-mediated signaling.
Cellular location follows from the absence of transmembrane segments and the soluble EF-hand scaffold: these sensors typically operate in the cytoplasm where Ca2+ transients are decoded and relayed. The soluble, full-length EF-hand composition and lack of targeting signals support a cytoplasmic residence, consistent with GO:0005737 cytoplasm.
Mechanistically, I hypothesize that Ca2+ binding across the EF-hand pair triggers a conformational rearrangement that exposes hydrophobic grooves and amphipathic helices, enabling transient capture of basic amphipathic target peptides. In Caenorhabditis elegans, likely partners include Ca2+/calmodulin-dependent kinases and phosphatases, myosin light chain pathways and actin–myosin assemblies, and other Ca2+-regulated channels or pumps. Through these interactions, the protein would tune cytoskeletal dynamics and phosphorylation states in response to Ca2+ signals, coordinating cytoplasmic signaling circuits with motility and stress responses.
A cytoplasmic calcium-sensing regulator that uses paired EF-hand motifs to bind Ca2+ and undergo conformational switching, thereby exposing target-recognition surfaces that modulate diverse effector proteins. By decoding transient calcium signals, it tunes kinase and phosphatase activities and cytoskeletal assemblies to propagate intracellular signaling in the cytoplasm of Caenorhabditis elegans.
Calmodulin mediates the control of a large number of enzymes, ion channels, and other proteins by Ca(2+).
IPR011992, homologous_superfamily) — residues 2-147IPR050230, family) — residues 2-148IPR002048, domain) — residues 8-149IPR018247, binding_site) — residues 21-142Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), protein binding (GO:0005515)
Biological Process: biological_process (GO:0008150), locomotion (GO:0040011), biological regulation (GO:0065007), localization (GO:0051179), response to stimulus (GO:0050896), regulation of biological process (GO:0050789), reproductive process (GO:0022414), developmental process (GO:0032502), cellular process (GO:0009987), negative regulation of biological process (GO:0048519), reproduction (GO:0000003), multicellular organismal process (GO:0032501), response to external stimulus (GO:0009605), cellular localization (GO:0051641), anatomical structure development (GO:0048856), multicellular organism development (GO:0007275), cell motility (GO:0048870), response to chemical (GO:0042221), establishment or maintenance of cell polarity (GO:0007163), meiotic cell cycle (GO:0051321), regulation of metabolic process (GO:0019222), taxis (GO:0042330), cell cycle process (GO:0022402), regulation of localization (GO:0032879), regulation of cellular process (GO:0050794), cell cycle (GO:0007049), establishment of localization (GO:0051234), cellular component organization or biogenesis (GO:0071840), meiotic cell cycle process (GO:1903046), microtubule-based process (GO:0007017), organelle localization (GO:0051640), negative regulation of metabolic process (GO:0009892), regulation of cell cycle (GO:0051726), establishment of cell polarity (GO:0030010), regulation of cell death (GO:0010941), spindle localization (GO:0051653), establishment of organelle localization (GO:0051656), negative regulation of macromolecule metabolic process (GO:0010605), regulation of cellular localization (GO:0060341), transport (GO:0006810), establishment of localization in cell (GO:0051649), regulation of macromolecule metabolic process (GO:0060255), cellular component organization (GO:0016043), embryo development (GO:0009790), microtubule cytoskeleton organization (GO:0000226), cell migration (GO:0016477), chemotaxis (GO:0006935), establishment of spindle localization (GO:0051293), regulation of programmed cell death (GO:0043067), positive chemotaxis (GO:0050918), vesicle-mediated transport (GO:0016192), regulation of protein localization (GO:0032880), establishment of spindle orientation (GO:0051294), organelle organization (GO:0006996), negative regulation of gene expression (GO:0010629), regulation of gene expression (GO:0010468), embryo development ending in birth or egg hatching (GO:0009792), cytoskeleton organization (GO:0007010), regulation of apoptotic process (GO:0042981), phagocytosis (GO:0006909), apoptotic cell clearance (GO:0043277)
Cellular Component: cellular_component (GO:0005575), cellular anatomical entity (GO:0110165), microtubule organizing center (GO:0005815), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), envelope (GO:0031975), membrane (GO:0016020), cell periphery (GO:0071944), endomembrane system (GO:0012505), organelle membrane (GO:0031090), organelle envelope (GO:0031967), nuclear envelope (GO:0005635), centrosome (GO:0005813), intracellular organelle (GO:0043229), membrane-bounded organelle (GO:0043227), non-membrane-bounded organelle (GO:0043228), nuclear membrane (GO:0031965), intracellular membrane-bounded organelle (GO:0043231), intracellular non-membrane-bounded organelle (GO:0043232), cytoskeleton (GO:0005856), spindle (GO:0005819), nucleus (GO:0005634), mitotic spindle (GO:0072686), microtubule cytoskeleton (GO:0015630)
Generated by BioReason
Source: cmd-1-bioreason-rl-predictions.md
The BioReason functional summary states:
A cytoplasmic calcium-sensing regulator that uses paired EF-hand motifs to bind Ca2+ and undergo conformational switching, thereby exposing target-recognition surfaces that modulate diverse effector proteins. By decoding transient calcium signals, it tunes kinase and phosphatase activities and cytoskeletal assemblies to propagate intracellular signaling in the cytoplasm of Caenorhabditis elegans.
This is an accurate and well-constructed summary. The curated review confirms that cmd-1 encodes the sole C. elegans calmodulin with four functional calcium-binding sites, and its core functions are calcium ion binding (GO:0005509), calcium-dependent protein binding (GO:0048306), and enzyme regulator activity (GO:0030234). The BioReason summary captures all three of these core molecular activities:
The cytoplasmic localization call is correct (GO:0005737 is accepted in the curated review).
The summary is slightly incomplete in that it does not mention the specific C. elegans biology: CMD-1's roles at spindle poles and centrosomes during cell division, meiotic spindle orientation, and the neuronal chemotaxis phenotype. However, since these are classified as non-core functions in the curated review, the omission is minor.
Comparison with interpro2go:
The interpro2go annotation (GO_REF:0000002) assigns GO:0005509 (calcium ion binding). BioReason correctly reproduces this but goes meaningfully beyond it by describing the calcium-dependent conformational switching and effector modulation, which corresponds to GO:0048306 (calcium-dependent protein binding) and GO:0030234 (enzyme regulator activity) -- terms from IBA annotations, not interpro2go. This shows genuine added value over pure domain-based annotation.
The trace provides a clean mechanistic chain from EF-hand architecture to calcium binding to effector regulation. The reasoning about calmodulin-like sensor behavior and the hypothesis about CaM-dependent kinases and phosphatases as interaction partners are well-calibrated.
id: O16305
gene_symbol: cmd-1
product_type: PROTEIN
status: DRAFT
taxon:
id: NCBITaxon:6239
label: Caenorhabditis elegans
description: >-
cmd-1 encodes the single Caenorhabditis elegans calmodulin, a small EF-hand
calcium sensor with four functional calcium-binding sites. The conserved core
function is calcium-dependent binding and regulation of target proteins,
including enzymes and spindle-associated factors. Experimental work in worms
additionally places CMD-1 at spindle poles, centrosomes, the interphase
nuclear membrane, and cell-cell boundaries in early embryos, and supports
context-specific roles in meiotic spindle orientation, embryonic morphogenesis,
apoptosis-related phenotypes, and neuronal chemotaxis. Falcon deep research
further documents concrete downstream effector contexts: CMD-1 is the Ca2+/CaM
activator component of the calcineurin phosphatase complex (with TAX-6 and
CNB-1), it sets a transcriptionally controlled, limiting level of neuronal
excitability, and it couples intestinal epithelial Ca2+ influx to NHX-6
activation in a gut-to-neuron host-defense pathway. Current GOA for cmd-1
contains no ISO annotations; the transfer-style annotations are IBA/IEA rather
than ISO, so this ISO-focused pass mainly evaluates whether those orthology-
derived calls are appropriately conservative.
existing_annotations:
- term:
id: GO:0005509
label: calcium ion binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: >-
This phylogenetically inferred annotation matches the defining biochemical
property of calmodulin family proteins. cmd-1 is the sole worm calmodulin,
UniProt records four functional calcium-binding sites, and no conflicting
evidence exists.
action: ACCEPT
reason: >-
Calcium ion binding is a conserved and central calmodulin activity, so the
orthology-based transfer is well supported and represents core function.
supported_by:
- reference_id: file:worm/cmd-1/cmd-1-uniprot.txt
supporting_text: This protein has four functional calcium-binding sites.
- reference_id: file:worm/cmd-1/cmd-1-deep-research-falcon.md
supporting_text: >-
encoding the Ca2+-binding messenger protein **CMD-1**
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: >-
Cytoplasmic localization is consistent with cmd-1 being a broadly acting
soluble calcium sensor. Experimental work in embryos also places CMD-1 on
spindle/centrosomal structures and other non-nuclear sites, which is
compatible with a general cytoplasmic annotation.
action: ACCEPT
reason: >-
Cytoplasm is a correct high-level cellular location for calmodulin and is
sufficiently general to retain as a core localization term.
supported_by:
- reference_id: file:worm/cmd-1/cmd-1-uniprot.txt
supporting_text: 'DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.'
- term:
id: GO:0030234
label: enzyme regulator activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: >-
Calmodulin-Ca2+ complexes regulate multiple enzyme classes, including
kinases and phosphatases, and UniProt explicitly describes cmd-1 as a
mediator of enzyme control. The term is broad, but it captures a genuine
conserved molecular role.
action: ACCEPT
reason: >-
Although general, enzyme regulator activity is an appropriate conserved
summary term for calmodulin and reflects core function rather than a
lineage-specific phenotype. Falcon deep research identifies a concrete
worm enzyme target: CMD-1 is the Ca2+/CaM activator subunit of the
calcineurin phosphatase complex (TAX-6 catalytic, CNB-1 regulatory).
supported_by:
- reference_id: file:worm/cmd-1/cmd-1-uniprot.txt
supporting_text: >-
Calmodulin mediates the control of a large number of enzymes, ion
channels and other proteins by Ca(2+).
- reference_id: file:worm/cmd-1/cmd-1-deep-research-falcon.md
supporting_text: >-
CMD-1 is part of the calcineurin activation complex (TAX-6/CNB-1/CMD-1)
- term:
id: GO:0000226
label: microtubule cytoskeleton organization
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: >-
The transfer is plausible because worm experiments support CMD-1 roles in
spindle organization and spindle orientation. However, the specific
evidence is tied to cell-division contexts rather than to a universally
defining calmodulin function.
action: KEEP_AS_NON_CORE
reason: >-
Retain the annotation as valid but non-core because it reflects a real,
experimentally supported spindle phenotype without being the central
conserved biochemical identity of the gene. Falcon deep research confirms
this is a recurring spindle-pole module function spanning multiple studies.
supported_by:
- reference_id: PMID:19219036
supporting_text: >-
ASPM-1, together with calmodulin (CMD-1), promotes meiotic spindle
organization
- reference_id: file:worm/cmd-1/cmd-1-deep-research-falcon.md
supporting_text: >-
CMD-1 acts with ASPM-1/LIN-5 to recruit dynein and drive meiotic spindle
rotation
- term:
id: GO:0005509
label: calcium ion binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: >-
InterPro-derived calcium ion binding agrees with the IBA call and with the
well-established EF-hand architecture of calmodulin.
action: ACCEPT
reason: >-
This is a correct electronic annotation for a canonical EF-hand calcium-
binding protein and matches core function.
supported_by:
- reference_id: file:worm/cmd-1/cmd-1-uniprot.txt
supporting_text: This protein has four functional calcium-binding sites.
- term:
id: GO:0072686
label: mitotic spindle
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: >-
The ARBA localization is consistent with direct experimental embryo data
showing CMD-1 accumulation on spindle structures. It is a correct but
context-specific localization.
action: KEEP_AS_NON_CORE
reason: >-
Mitotic spindle localization is supported, but it is not a universal core
localization for calmodulin across all contexts.
supported_by:
- reference_id: file:worm/cmd-1/cmd-1-deep-research-falcon.md
supporting_text: >-
CMD-1 acts with ASPM-1/LIN-5 to recruit dynein and drive meiotic spindle
rotation
- term:
id: GO:0010629
label: negative regulation of gene expression
evidence_type: IMP
original_reference_id: PMID:34499028
review:
summary: >-
PMID:34499028 supports a specific autoregulatory loop in which high CMD-1
levels repress expression from the cmd-1 promoter through CAMT-1. That is
more limited than generic negative regulation of gene expression.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The paper supports context-specific feedback on cmd-1 transcription, not a
broad generic role in repressing gene expression across targets.
supported_by:
- reference_id: PMID:34499028
supporting_text: high levels of CMD-1 can repress expression from the cmd-1 promoter
- term:
id: GO:0050918
label: positive chemotaxis
evidence_type: IMP
original_reference_id: PMID:34499028
review:
summary: >-
Neuronal reduction of cmd-1 contributes to chemotaxis defects, and
supplementing neuronal CMD-1 rescues attraction to several cues in the
CAMT-1 regulatory context examined in the paper.
action: KEEP_AS_NON_CORE
reason: >-
The phenotype is real but represents a specialized neuronal/behavioral
context rather than the core conserved role of calmodulin. Falcon deep
research underscores that neuronal CMD-1 abundance is a limiting,
transcriptionally controlled determinant of sensory-neuron excitability
and chemotaxis behavior.
supported_by:
- reference_id: PMID:34499028
supporting_text: restored normal chemotaxis toward salt, benzaldehyde, and diacetyl
- reference_id: file:worm/cmd-1/cmd-1-deep-research-falcon.md
supporting_text: >-
reduced CaM levels are associated with hyperexcitable Ca2+ responses in
sensory neurons
- term:
id: GO:0009792
label: embryo development ending in birth or egg hatching
evidence_type: IMP
original_reference_id: PMID:14703012
review:
summary: >-
cmd-1 RNAi causes severe embryonic lethality with disturbed morphogenesis,
so the gene clearly contributes to successful embryogenesis.
action: KEEP_AS_NON_CORE
reason: >-
This broad developmental phenotype is supported experimentally, but it is a
pleiotropic consequence of depleting a global calcium sensor and should not
be treated as core function. Falcon deep research quantifies the strong
essentiality (~95% embryonic lethality by dsRNA injection) while framing it
as downstream of CMD-1's global Ca2+-sensor role.
supported_by:
- reference_id: PMID:14703012
supporting_text: RNAi microinjection approach results in a severe embryonic lethal phenotype
- reference_id: file:worm/cmd-1/cmd-1-deep-research-falcon.md
supporting_text: >-
cmd-1 knockdown produced **~95% embryonic lethality**
- term:
id: GO:0005813
label: centrosome
evidence_type: IDA
original_reference_id: PMID:17716666
review:
summary: >-
Full-text evidence from PMID:17716666 shows GFP-tagged CMD-1 accumulation
at centrosomes in early embryos.
action: KEEP_AS_NON_CORE
reason: >-
The localization is directly observed and valid, but it is a cell-division
context rather than a core pan-context localization.
- term:
id: GO:0031965
label: nuclear membrane
evidence_type: IDA
original_reference_id: PMID:17716666
review:
summary: >-
The same embryo localization study reports CMD-1 at the interphase nuclear
membrane.
action: KEEP_AS_NON_CORE
reason: >-
The annotation is experimentally supported but context-specific and not a
primary summary of calmodulin function.
- term:
id: GO:0071944
label: cell periphery
evidence_type: IDA
original_reference_id: PMID:17716666
review:
summary: >-
PMID:17716666 reports CMD-1 at the borders of abutting cells in embryos,
which justifies a general cell periphery term.
action: KEEP_AS_NON_CORE
reason: >-
Direct localization supports the term, but this is again a non-core,
context-dependent localization.
- term:
id: GO:0072686
label: mitotic spindle
evidence_type: IDA
original_reference_id: PMID:17716666
review:
summary: >-
Direct imaging shows CMD-1 on spindle structures and not at the cleavage
furrow in early embryos.
action: KEEP_AS_NON_CORE
reason: >-
Correct experimental localization, but specialized to embryonic cell
division rather than a core location.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19219036
review:
summary: >-
PMID:19219036 places CMD-1 in an ASPM-1/LIN-5 spindle-pole complex, so a
physical interaction claim is credible. However, protein binding is too
generic for calmodulin and loses the informative calcium-dependent nature
of its target interactions.
action: MODIFY
reason: >-
The interaction evidence should be retained, but the annotation should use
a more informative calmodulin-appropriate term rather than generic protein
binding.
proposed_replacement_terms:
- id: GO:0048306
label: calcium-dependent protein binding
- term:
id: GO:0032880
label: regulation of protein localization
evidence_type: IMP
original_reference_id: PMID:19219036
review:
summary: >-
The meiosis study shows CMD-1 promotes accumulation of LIN-5 at meiotic and
mitotic spindle poles, which is an experimentally grounded protein
localization phenotype.
action: KEEP_AS_NON_CORE
reason: >-
This process annotation is valid but reflects a specific spindle-pole
context, not cmd-1's central conserved biochemical identity. Falcon deep
research reinforces that the CMD-1/LIN-5/ASPM-1 module recruits dynein to
spindle poles, and that this recruitment is gated by CDK-1.
supported_by:
- reference_id: PMID:19219036
supporting_text: >-
promotes meiotic spindle organization and the accumulation of LIN-5 at
meiotic and mitotic spindle poles
- reference_id: file:worm/cmd-1/cmd-1-deep-research-falcon.md
supporting_text: >-
CDK-1 inhibits spindle rotation by blocking the interaction between the
**CMD-1–LIN-5–ASPM-1** module and **DHC-1/dynein**
- term:
id: GO:0051296
label: establishment of meiotic spindle orientation
evidence_type: IMP
original_reference_id: PMID:19219036
review:
summary: >-
The paper directly concludes that LIN-5, ASPM-1, CMD-1 and dynein are
required for spindle rotation during maternal meiosis.
action: KEEP_AS_NON_CORE
reason: >-
Strong experimental support exists, but the process is specialized rather
than core to calmodulin across contexts. Falcon deep research corroborates
this with an independent follow-up study (Ellefson & McNally 2011) showing
cmd-1(RNAi) abolishes meiosis I spindle rotation.
supported_by:
- reference_id: PMID:19219036
supporting_text: >-
Spindle rotation during maternal meiosis is independent of GPR-1/2 and
Galpha, yet requires LIN-5, ASPM-1, CMD-1 and dynein
- reference_id: file:worm/cmd-1/cmd-1-deep-research-falcon.md
supporting_text: >-
cmd-1(RNAi) abolished meiosis I spindle rotation
- term:
id: GO:0051296
label: establishment of meiotic spindle orientation
evidence_type: IGI
original_reference_id: PMID:19219036
review:
summary: >-
The genetic interaction-based version of the same process annotation is
consistent with the paper's functional dissection of the spindle-pole
complex.
action: KEEP_AS_NON_CORE
reason: >-
Retain as non-core for the same reason as the IMP entry: direct support,
but specialized biology.
supported_by:
- reference_id: PMID:19219036
supporting_text: >-
Spindle rotation during maternal meiosis is independent of GPR-1/2 and
Galpha, yet requires LIN-5, ASPM-1, CMD-1 and dynein
- term:
id: GO:0016477
label: cell migration
evidence_type: IMP
original_reference_id: PMID:14703012
review:
summary: >-
cmd-1 RNAi embryos show aberrant cell migration patterns according to the
abstract, supporting a migration-related phenotype.
action: KEEP_AS_NON_CORE
reason: >-
This is a pleiotropic developmental phenotype observed after strong loss of
a global calcium sensor, so it should be retained only as non-core.
supported_by:
- reference_id: PMID:14703012
supporting_text: Embryos show disturbed morphogenesis, aberrant cell migration patterns
- term:
id: GO:0042981
label: regulation of apoptotic process
evidence_type: IMP
original_reference_id: PMID:14703012
review:
summary: >-
The abstract reports multiple defects in apoptosis after cmd-1 depletion,
which supports involvement in apoptosis-related regulation.
action: KEEP_AS_NON_CORE
reason: >-
The phenotype is supported, but it is broad and likely pleiotropic rather
than a core defining function of calmodulin.
supported_by:
- reference_id: PMID:14703012
supporting_text: multiple defects in apoptosis
- term:
id: GO:0043277
label: apoptotic cell clearance
evidence_type: IMP
original_reference_id: PMID:14703012
review:
summary: >-
The accessible abstract supports apoptosis defects, but it does not clearly
distinguish cell corpse clearance/engulfment from upstream apoptosis
defects.
action: UNDECIDED
reason: >-
This specific term may be correct, but the currently accessible evidence is
insufficiently specific to review it confidently.
- term:
id: GO:0051726
label: regulation of cell cycle
evidence_type: IMP
original_reference_id: PMID:14703012
review:
summary: >-
Hyperproliferation in cmd-1 RNAi embryos is consistent with cell-cycle
dysregulation after depletion of calmodulin.
action: KEEP_AS_NON_CORE
reason: >-
The phenotype is experimentally supported, but it is a broad developmental
consequence rather than a core molecular role.
supported_by:
- reference_id: PMID:14703012
supporting_text: a striking hyperproliferation of cells
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO terms
findings:
- statement: InterPro family mapping supports the calcium ion binding annotation
for EF-hand calmodulin proteins.
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings:
- statement: cmd-1 has no current ISO annotations in GOA; the orthology-style
transfer set for this gene is IBA rather than ISO.
- statement: The IBA annotations capture conserved calmodulin properties such as
calcium ion binding, cytoplasmic localization, and broad enzyme-regulatory
function.
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings:
- statement: ARBA assigns mitotic spindle localization, which is consistent with
direct embryo localization data.
- id: PMID:14703012
title: Functional analysis of the single calmodulin gene in the nematode Caenorhabditis
elegans by RNA interference and 4-D microscopy.
findings:
- statement: cmd-1 RNAi causes severe embryonic lethality with disturbed morphogenesis.
supporting_text: >-
RNAi microinjection approach results in a severe embryonic lethal phenotype.
Embryos show disturbed morphogenesis
- statement: cmd-1 RNAi embryos show aberrant cell migration patterns,
hyperproliferation, and multiple defects in apoptosis.
supporting_text: >-
Embryos show disturbed morphogenesis, aberrant cell migration patterns, a
striking hyperproliferation of cells and multiple defects in apoptosis.
- id: PMID:17716666
title: Cytokinesis is not controlled by calmodulin or myosin light chain kinase
in the Caenorhabditis elegans early embryo.
findings:
- statement: cmd-1 depletion does not block cytokinesis in early embryos.
supporting_text: >-
RNA mediated interference against C. elegans calmodulin and candidate MLCKs
had no effect on cytokinesis in wild-type or RhoK mutant embryos
- id: PMID:19219036
title: NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle
rotation independently of cortical LIN-5/GPR/Galpha.
findings:
- statement: CMD-1 works with ASPM-1 and LIN-5 in a spindle-pole complex.
supporting_text: >-
ASPM-1, together with calmodulin (CMD-1), promotes meiotic spindle
organization and the accumulation of LIN-5 at meiotic and mitotic spindle
poles.
- statement: CMD-1 promotes meiotic spindle organization and spindle rotation
during maternal meiosis.
supporting_text: >-
Spindle rotation during maternal meiosis is independent of GPR-1/2 and
Galpha, yet requires LIN-5, ASPM-1, CMD-1 and dynein.
- statement: CMD-1 promotes accumulation of LIN-5 at meiotic and mitotic spindle
poles.
supporting_text: >-
ASPM-1, together with calmodulin (CMD-1), promotes meiotic spindle
organization and the accumulation of LIN-5 at meiotic and mitotic spindle
poles.
- id: PMID:34499028
title: Neuronal calmodulin levels are controlled by CAMTA transcription factors.
findings:
- statement: cmd-1 expression is reduced across multiple neuronal cell types in
camt-1 mutants.
supporting_text: >-
cmd-1 was one of only two genes whose expression was reduced in all four
neural profiles relative to WT controls.
- statement: High CMD-1 levels can repress expression from the cmd-1 promoter,
indicating autoregulatory feedback.
supporting_text: high levels of CMD-1 can repress expression from the cmd-1 promoter
- statement: Supplementing neuronal CMD-1 rescues chemotaxis and neuronal
calcium-signaling defects in the CAMT-1 regulatory context.
supporting_text: restored normal chemotaxis toward salt, benzaldehyde, and diacetyl
- id: PMID:17854888
title: Ca(2+)/Calmodulin-binding proteins from the C. elegans proteome.
findings:
- statement: Calmodulin is described as the primary calcium sensor that regulates
a wide variety of cellular processes in eukaryotes.
supporting_text: >-
Calmodulin (CaM) is the primary Ca(2+)-sensor that regulates a wide variety
of cellular processes in eukaryotes.
- statement: The study identified multiple Ca2+/calmodulin-binding proteins from
the C. elegans proteome, reinforcing CMD-1's role as a broad calcium-
dependent target binder.
supporting_text: >-
The method allowed the identification of 9 known and 47 previously
uncharacterized Ca(2+)-dependent CaM-binding proteins from the adult worm
proteome.
- id: file:worm/cmd-1/cmd-1-uniprot.txt
title: UniProt record for C. elegans cmd-1
findings:
- statement: UniProt records four functional calcium-binding sites in CMD-1.
- statement: UniProt states that calmodulin mediates control of many enzymes, ion
channels, and other proteins by Ca2+.
- id: PMID:21690306
title: CDK-1 inhibits meiotic spindle shortening and dynein-dependent spindle rotation
in C. elegans.
findings:
- statement: CDK-1 gates meiotic spindle rotation by blocking dynein association
with microtubules and with the LIN-5-ASPM-1 (with CMD-1) module at spindle poles.
supporting_text: >-
rotation by inhibiting dynein association with microtubules and with
reference_section_type: ABSTRACT
- statement: APC-driven CDK-1 inactivation relieves this block, allowing dynein
accumulation and spindle rotation.
supporting_text: >-
LIN-5-ASPM-1 at meiotic spindle poles and that the APC promotes spindle rotation
reference_section_type: ABSTRACT
- id: PMID:31944606
title: Caenorhabditis elegans phosphatase complexes in UniProtKB and Complex Portal.
findings:
- statement: Expert curation places CMD-1 (calmodulin) in the C. elegans calcineurin
phosphatase complex together with the catalytic subunit TAX-6 and regulatory
subunit CNB-1, consistent with canonical Ca2+/CaM-dependent calcineurin activation.
supporting_text: >-
biological significance of phosphatase
reference_section_type: ABSTRACT
- id: PMID:36920509
title: Human calmodulin mutations cause arrhythmia and affect neuronal function in
C. elegans.
findings:
- statement: Humanized cmd-1 alleles carrying pathogenic human calmodulin variants
(N54I, D96V) disrupt rhythmic behaviors (pharynx pumping and the defecation motor
program), providing an in vivo CMD-1 functional readout for calmodulinopathy.
supporting_text: >-
calmodulin mutations N54I and D96V can be recapitulated in disruption of two
reference_section_type: ABSTRACT
- statement: The same variants affect neuronal function differently (D96V sensitizes
the neuromuscular junction; N54I is protective), and N98S impairs chemosensing
without affecting rhythmic behavior.
supporting_text: >-
Whereas D96V sensitizes signaling at the neuromuscular junction, N54I has
reference_section_type: ABSTRACT
- id: PMID:41888139
title: Proton signaling links epithelial sensing to neural control of host defense
in C. elegans.
findings:
- statement: In intestinal epithelial cells, pathogen-stimulated Ca2+ influx through
GON-2 activates the Na+/H+ exchanger NHX-6 via the calmodulin CMD-1, driving
basolateral proton release that signals to cholinergic neurons through ASIC-1.
supporting_text: >-
exchanger NHX-6 via the calmodulin CMD-1 to drive basolateral proton release.
reference_section_type: ABSTRACT
- id: file:worm/cmd-1/cmd-1-deep-research-falcon.md
title: Falcon deep research report for C. elegans cmd-1 (calmodulin)
findings:
- statement: cmd-1 is the single C. elegans calmodulin gene encoding the conserved
intracellular Ca2+ sensor CMD-1.
supporting_text: >-
encoding the Ca2+-binding messenger protein **CMD-1**
- statement: CMD-1 acts within a spindle-pole module with ASPM-1 and LIN-5 to recruit
dynein and drive meiotic spindle rotation; cmd-1(RNAi) abolishes meiosis I spindle
rotation.
supporting_text: >-
CMD-1 acts with ASPM-1/LIN-5 to recruit dynein and drive meiotic spindle
rotation
- statement: CMD-1 is the Ca2+/CaM activator component of the worm calcineurin
phosphatase complex (TAX-6 catalytic, CNB-1 regulatory).
supporting_text: >-
CMD-1 is part of the calcineurin activation complex (TAX-6/CNB-1/CMD-1)
- statement: Neuronal CMD-1 abundance is a limiting, transcriptionally controlled
determinant of sensory-neuron excitability and behavior.
supporting_text: >-
reduced CaM levels are associated with hyperexcitable Ca2+ responses in
sensory neurons
- statement: CMD-1 couples intestinal epithelial Ca2+ influx to NHX-6 activation and
proton release in a gut-to-neuron host-defense pathway.
supporting_text: >-
CMD-1 couples Ca2+ influx in intestinal epithelial cells to NHX-6 activation
and proton release
core_functions:
- description: >-
Primary EF-hand calcium sensor that binds calcium ions through four conserved
sites and acts as the biochemical core of worm calmodulin function.
molecular_function:
id: GO:0005509
label: calcium ion binding
locations:
- id: GO:0005737
label: cytoplasm
supported_by:
- reference_id: file:worm/cmd-1/cmd-1-uniprot.txt
supporting_text: This protein has four functional calcium-binding sites.
- description: >-
Calcium-loaded CMD-1 binds target proteins and mediates their regulation;
this includes conserved Ca2+/CaM target binding across the worm proteome and
spindle-pole associated interactions in embryos.
molecular_function:
id: GO:0048306
label: calcium-dependent protein binding
locations:
- id: GO:0005737
label: cytoplasm
supported_by:
- reference_id: PMID:17854888
supporting_text: >-
Calmodulin (CaM) is the primary Ca(2+)-sensor that regulates a wide variety
of cellular processes in eukaryotes.
- reference_id: PMID:19219036
supporting_text: >-
ASPM-1, together with calmodulin (CMD-1), promotes meiotic spindle
organization and the accumulation of LIN-5 at meiotic and mitotic spindle
poles.
- description: >-
Calmodulin-Ca2+ acts as a broad enzyme regulator, stimulating downstream
kinase and phosphatase targets rather than serving as an enzyme itself. A
concrete worm example is the calcineurin phosphatase complex, in which CMD-1
is the Ca2+/CaM activator subunit alongside catalytic TAX-6 and regulatory
CNB-1.
molecular_function:
id: GO:0030234
label: enzyme regulator activity
locations:
- id: GO:0005737
label: cytoplasm
supported_by:
- reference_id: file:worm/cmd-1/cmd-1-uniprot.txt
supporting_text: >-
Calmodulin mediates the control of a large number of enzymes, ion channels
and other proteins by Ca(2+).
- reference_id: file:worm/cmd-1/cmd-1-deep-research-falcon.md
supporting_text: >-
CMD-1 is part of the calcineurin activation complex (TAX-6/CNB-1/CMD-1)
proposed_new_terms: []
suggested_questions:
- question: Which direct CMD-1 target proteins at spindle poles are most important
for the meiotic spindle orientation phenotype in embryos?
- question: Which apoptosis and cell-migration phenotypes after cmd-1 depletion are
direct CMD-1-dependent processes versus secondary consequences of broad calcium
signaling collapse?
- question: Should calmodulin-family curation in nematodes explicitly add
calcium-dependent protein binding where older annotations still use generic
protein binding?
suggested_experiments:
- description: Endogenous tagged CMD-1 affinity purification or proximity labeling
under Ca2+-bound and Ca2+-free conditions to define direct embryo and neuronal
target proteins.
- description: Rescue cmd-1 loss with EF-hand calcium-binding mutants to separate
calcium sensing from possible scaffolding/localization roles at spindle poles.
- description: Tissue-specific depletion or rescue in embryos versus neurons to
distinguish direct spindle and chemotaxis functions from pleiotropic systemic
effects.