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

Overview

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.

publication date

  • May 6, 2017

Research

keywords

  • Caenorhabditis elegans Proteins
  • Calcium
  • Calcium Channels, L-Type
  • Cations, Divalent
  • Cyclic AMP Response Element-Binding Protein
  • Transcription Factors

Identity

PubMed Central ID

  • PMC5432211

Scopus Document Identifier

  • 85019845856

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2015.11.023

PubMed ID

  • 28477407

Additional Document Info

volume

  • 6