Shank is a dose-dependent regulator of Cav1 calcium current and CREB target expression
- Massachusetts General Hospital, United States
- University of California, San Francisco, United States
- Stanford School of Medicine, United States
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.
Article and author information
Author details
Katherine L Thompson-Peer
Funding
National Institute of Neurological Disorders and Stroke (NS32196)
- Joshua M Kaplan
Simons Foundation (SF273555)
- Joshua M Kaplan
Nancy Lurie Marks Family Foundation
- Edward Pym
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Graeme W Davis, University of California, San Francisco, United States
Version history
- Received: June 19, 2016
- Accepted: April 18, 2017
- Accepted Manuscript published: May 6, 2017 (version 1)
- Version of Record published: May 15, 2017 (version 2)
Copyright
© 2017, Pym et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Shank is a dose-dependent regulator of Cav1 calcium current and CREB target expression
eLife 6:e18931.
https://doi.org/10.7554/eLife.18931
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