1. Shank is a dose-dependent regulator of Cav1 calcium current and CREB target expression.
- Author
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Pym, Edward, Sasidharan, Nikhil, Thompson-Peer, Katherine L, Simon, David J, Anselmo, Anthony, Sadreyev, Ruslan, Hall, Qi, Nurrish, Stephen, and Kaplan, Joshua M
- Subjects
Muscles ,Animals ,Caenorhabditis elegans ,Cations ,Divalent ,Calcium ,Calcium Channels ,L-Type ,Caenorhabditis elegans Proteins ,Transcription Factors ,Cyclic AMP Response Element-Binding Protein ,C. elegans ,CREB ,L-type channel ,SHN-1 ,Shank ,autism ,neuroscience ,Cations ,Divalent ,Calcium Channels ,L-Type ,Pediatric ,Neurosciences ,Intellectual and Developmental Disabilities ,Brain Disorders ,Autism ,Schizophrenia ,Genetics ,Mental Health ,2.1 Biological and endogenous factors ,1.1 Normal biological development and functioning ,Biochemistry and Cell Biology - 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.
- Published
- 2017