Neuronal calmodulin levels are controlled by CAMTA transcription factors

eLife

Yvonne Vallis¹  Mario de Bono¹  Thanh Thi Vuong-Brender²  Sean Flynn³ 

[1] Cell Biology Division, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom;Cell Biology Division, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom;Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria;Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria;

关键词: neuronal excitability;    calmodulin;    expression profiling;    transcription factors;    chip seq;    Drosophila;    C. elegans;   

DOI  :  10.7554/eLife.68238

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY