Neuronal calmodulin levels are controlled by CAMTA transcription factors

Elife. 2021 Sep 9:10:e68238. doi: 10.7554/eLife.68238.


The ubiquitous Ca2+ sensor calmodulin (CaM) binds and regulates many proteins, including ion channels, CaM kinases, and calcineurin, according to Ca2+-CaM levels. What regulates neuronal CaM levels, is, however, unclear. CaM-binding transcription activators (CAMTAs) are ancient proteins expressed broadly in nervous systems and whose loss confers pleiotropic behavioral defects in flies, mice, and humans. Using Caenorhabditis elegans and Drosophila, we show that CAMTAs control neuronal CaM levels. The behavioral and neuronal Ca2+ signaling defects in mutants lacking camt-1, the sole C. elegans CAMTA, can be rescued by supplementing neuronal CaM. CAMT-1 binds multiple sites in the CaM promoter and deleting these sites phenocopies camt-1. Our data suggest CAMTAs mediate a conserved and general mechanism that controls neuronal CaM levels, thereby regulating Ca2+ signaling, physiology, and behavior.

Keywords: C. elegans; Drosophila; calmodulin; chip seq; expression profiling; genetics; genomics; neuronal excitability; neuroscience; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism
  • Calcineurin / metabolism
  • Calcium / metabolism
  • Calmodulin / metabolism*
  • Calmodulin-Binding Proteins / metabolism*
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Female
  • Gene Editing
  • Gene Expression Regulation
  • Humans
  • Male
  • Mice
  • Neurons / metabolism*
  • Protein Binding
  • Signal Transduction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism*
  • Transcriptome


  • CAMTA protein, Drosophila
  • Calmodulin
  • Calmodulin-Binding Proteins
  • Drosophila Proteins
  • Trans-Activators
  • Transcription Factors
  • Calcineurin
  • Calcium

Associated data

  • GEO/GSE164671