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The ubiquitous Ca 2+ sensor calmodulin (CaM) binds and regulates many proteins, including ion channels, CaM kinases, and calcineurin, according to Ca 2+ -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 Ca 2+ 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 Ca 2+ signaling, physiology, and behavior.

Competing Interests: TV, SF, YV, Md No competing interests declared

Titel:	Neuronal calmodulin levels are controlled by CAMTA transcription factors.
Autor/in / Beteiligte Person:	Vuong-Brender, TT ; Flynn, S ; Vallis, Y ; de Bono M
Link:	Zum Volltext
Zeitschrift:	ELife, Jg. 10 (2021-09-09)
Veröffentlichung:	Cambridge, UK : eLife Sciences Publications, Ltd., 2012-, 2021
Medientyp:	academicJournal
ISSN:	2050-084X (electronic)
DOI:	10.7554/eLife.68238
Schlagwort:	Animals Caenorhabditis elegans metabolism Calcineurin metabolism Calcium metabolism Drosophila metabolism Drosophila Proteins genetics Drosophila melanogaster Female Gene Editing Gene Expression Regulation Humans Male Mice Protein Binding Signal Transduction Trans-Activators genetics Transcriptome Calmodulin metabolism Calmodulin-Binding Proteins metabolism Drosophila Proteins metabolism Neurons metabolism Trans-Activators metabolism Transcription Factors metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Elife] 2021 Sep 09; Vol. 10. <i>Date of Electronic Publication: </i>2021 Sep 09. MeSH Terms: Calmodulin / metabolism ; Calmodulin-Binding Proteins / metabolism ; Drosophila Proteins / metabolism ; Neurons / metabolism ; Trans-Activators / metabolism ; Transcription Factors / metabolism ; Animals ; Caenorhabditis elegans / metabolism ; Calcineurin / metabolism ; Calcium / metabolism ; Drosophila / metabolism ; Drosophila Proteins / genetics ; Drosophila melanogaster ; Female ; Gene Editing ; Gene Expression Regulation ; Humans ; Male ; Mice ; Protein Binding ; Signal Transduction ; Trans-Activators / genetics ; Transcriptome References: Biophys J. 2008 Dec 15;95(12):6002-15. (PMID: 18820232) ; Nature. 2009 Feb 26;457(7233):1154-8. (PMID: 19122675) ; J Biol Chem. 2002 Jun 14;277(24):21851-61. 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(PMID: 14711416) Grant Information: United Kingdom WT_ Wellcome Trust; MC_U105178786 United Kingdom MRC_ Medical Research Council; 209504/Z/17/Z United Kingdom WT_ Wellcome Trust Contributed Indexing: Keywords: C. elegans; Drosophila; calmodulin; chip seq; expression profiling; genetics; genomics; neuronal excitability; neuroscience; transcription factors Molecular Sequence: GEO GSE164671 Substance Nomenclature: 0 (CAMTA protein, Drosophila) ; 0 (Calmodulin) ; 0 (Calmodulin-Binding Proteins) ; 0 (Drosophila Proteins) ; 0 (Trans-Activators) ; 0 (Transcription Factors) ; EC 3.1.3.16 (Calcineurin) ; SY7Q814VUP (Calcium) Entry Date(s): Date Created: 20210909 Date Completed: 20211028 Latest Revision: 20230329 Update Code: 20240513 PubMed Central ID: PMC8428840

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Neuronal calmodulin levels are controlled by CAMTA transcription factors.