Format

Send to

Choose Destination
Elife. 2017 May 6;6. pii: e18931. doi: 10.7554/eLife.18931.

Shank is a dose-dependent regulator of Cav1 calcium current and CREB target expression.

Author information

1
Department of Molecular Biology, Massachusetts General Hospital, Boston, United States.
2
Department of Neurobiology, Harvard Medical School, Boston, United States.
3
Program in Neuroscience, Harvard Medical School, Boston, 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.

KEYWORDS:

C. elegans; CREB; L-type channel; SHN-1; Shank; autism; neuroscience

PMID:
28477407
PMCID:
PMC5432211
DOI:
10.7554/eLife.18931
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center