| 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 | (pqac-00000001, pqac-00000005) |
| 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 | (pqac-00000004, pqac-00000006, pqac-00000011, pqac-00000013) |
| 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 | (pqac-00000011, pqac-00000013) |
| 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 | (pqac-00000019, pqac-00000020, pqac-00000022) |
| 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 | (pqac-00000008) |
| 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 | (pqac-00000007) |
| 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 | (pqac-00000010) |


*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.*