RRC ID 51387
Author Pym E, Sasidharan N, Thompson-Peer KL, Simon DJ, Anselmo A, Sadreyev R, Hall Q, Nurrish S, Kaplan JM.
Title Shank is a dose-dependent regulator of Cav1 calcium current and CREB target expression.
Journal Elife
Abstract Shank is a post-synaptic scaffolding protein that has many binding partners. Shank mutations and copy number variations (CNVs) are linked to several psychiatric disorders, and to synaptic and behavioral defects in mice. It is not known which Shank binding partners are responsible for these defects. Here we show that the C. elegans SHN-1/Shank binds L-type calcium channels and that increased and decreased shn-1 gene dosage alter L-channel current and activity-induced expression of a CRH-1/CREB transcriptional target (gem-4 Copine), which parallels the effects of human Shank copy number variations (CNVs) on Autism spectrum disorders and schizophrenia. These results suggest that an important function of Shank proteins is to regulate L-channel current and activity induced gene expression.
Volume 6
Published 2017-5-6
DOI 10.7554/eLife.18931
PII e18931
PMID 28477407
PMC PMC5432211
MeSH Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / metabolism* Calcium / metabolism* Calcium Channels, L-Type / metabolism* Cations, Divalent / metabolism* Cyclic AMP Response Element-Binding Protein / metabolism* Muscles / physiology Transcription Factors / metabolism*
IF 7.08
Times Cited 3
Resource
C.elegans tm488