Shank is a dose-dependent regulator of Ca<sub>v</sub>1 calcium current and CREB target expression.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28477407.
- Also identified by DOI 10.7554/eLife.18931 and PMC identifier 5432211.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>C. elegans</i> SHN-1/Shank binds L-type calcium channels and that increased and decreased <i>shn-1</i> gene dosage alter L-channel current and activity-induced expression of a CRH-1/CREB transcriptional target (<i>gem-4</i> 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.
Medical subject headings
- Caenorhabditis elegans Proteins
- Calcium
- Calcium Channels, L-Type
- Cations, Divalent
- Cyclic AMP Response Element-Binding Protein
- Transcription Factors