Shank is a dose-dependent regulator of Cav1 calcium current and CREB target expression.
Edward PymNikhil SasidharanKatherine L Thompson-PeerDavid J SimonAnthony AnselmoRuslan SadreyevQi HallStephen NurrishJoshua M KaplanPublished in: eLife (2017)
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.
Keyphrases
- copy number
- mitochondrial dna
- gene expression
- genome wide
- dna methylation
- poor prognosis
- binding protein
- autism spectrum disorder
- high glucose
- endothelial cells
- transcription factor
- diabetic rats
- type diabetes
- drug induced
- bipolar disorder
- long non coding rna
- metabolic syndrome
- skeletal muscle
- adipose tissue
- hiv testing
- antiretroviral therapy