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.
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this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
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We are interested in where in or outside the cell the gene product carries out its function.
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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.