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.
The authors thank the MRC-LMB Flow Cytometry facility and Imaging Service for support, the Cancer Research UK Cambridge Institute Genomics Core for Next Generation Sequencing, Julie Ahringer and Alex Appert for advice and technical help for ChIP-seq experiments, Paula Freire-Pritchett, Tim Stevens, and Gurpreet Ghattaoraya for RNA-seq and ChIP-seq analyses, Nikos Chronis for the TN-XL plasmid, Hong-Sheng Li and Daisuke Yamamoto for generously sending the tes2 and cro mutants, Daria Siekhaus for hosting the fly work, Michaela Misova for technical assistance. The authors are very grateful to Salihah Ece Sönmez for teaching us how to dissect, mount and stain Drosophila retinae. This work was supported by an Advanced ERC grant (269058 ACMO) and a Wellcome Investigator Award (209504/Z/17/Z) to MdB, and an IST Plus Fellowship to TV-B (Marie Sklodowska-Curie Agreement no 754411).
Vuong-Brender T, Flynn S, Vallis Y, de Bono M. Neuronal calmodulin levels are controlled by CAMTA transcription factors. eLife. 2021;10. doi:10.7554/eLife.68238
Vuong-Brender, T., Flynn, S., Vallis, Y., & de Bono, M. (2021). Neuronal calmodulin levels are controlled by CAMTA transcription factors. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.68238
Vuong-Brender, Thanh, Sean Flynn, Yvonne Vallis, and Mario de Bono. “Neuronal Calmodulin Levels Are Controlled by CAMTA Transcription Factors.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/eLife.68238.
T. Vuong-Brender, S. Flynn, Y. Vallis, and M. de Bono, “Neuronal calmodulin levels are controlled by CAMTA transcription factors,” eLife, vol. 10. eLife Sciences Publications, 2021.
Vuong-Brender T, Flynn S, Vallis Y, de Bono M. 2021. Neuronal calmodulin levels are controlled by CAMTA transcription factors. eLife. 10, e68238.
Vuong-Brender, Thanh, et al. “Neuronal Calmodulin Levels Are Controlled by CAMTA Transcription Factors.” ELife, vol. 10, e68238, eLife Sciences Publications, 2021, doi:10.7554/eLife.68238.
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