Neuronal calmodulin levels are controlled by CAMTA transcription factors.

Abstract

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 <i>Caenorhabditis elegans</i> and <i>Drosophila</i>, we show that CAMTAs control neuronal CaM levels. The behavioral and neuronal Ca²⁺ signaling defects in mutants lacking <i>camt-1,</i> the sole <i>C. elegans</i> CAMTA, can be rescued by supplementing neuronal CaM. CAMT-1 binds multiple sites in the CaM promoter and deleting these sites phenocopies <i>camt-1</i>. Our data suggest CAMTAs mediate a conserved and general mechanism that controls neuronal CaM levels, thereby regulating Ca²⁺ signaling, physiology, and behavior.