NDLI: Physical interaction of calmodulin with the 5-hydroxytryptamine2C receptor C-terminus is essential for G protein-independent, arrestin-dependent receptor signaling.

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Physical interaction of calmodulin with the 5-hydroxytryptamine2C receptor C-terminus is essential for G protein-independent, arrestin-dependent receptor signaling.

Content Provider	Semantic Scholar
Author	Labasque, Marilyne Reiter, Eric Bécamel, Carine Bockaert, Jöel Marin, Philippe
Copyright Year	2008
Abstract	The serotonin (5-hydroxytryptamine; 5-HT)(2C) receptor is a G protein-coupled receptor (GPCR) exclusively expressed in CNS that has been implicated in numerous brain disorders, including anxio-depressive states. Like many GPCRs, 5-HT(2C) receptors physically interact with a variety of intracellular proteins in addition to G proteins. Here, we show that calmodulin (CaM) binds to a prototypic Ca(2+)-dependent "1-10" CaM-binding motif located in the proximal region of the 5-HT(2C) receptor C-terminus upon receptor activation by 5-HT. Mutation of this motif inhibited both beta-arrestin recruitment by 5-HT(2C) receptor and receptor-operated extracellular signal-regulated kinase (ERK) 1,2 signaling in human embryonic kidney-293 cells, which was independent of G proteins and dependent on beta-arrestins. A similar inhibition was observed in cells expressing a dominant-negative CaM or depleted of CaM by RNA interference. Expression of the CaM mutant also prevented receptor-mediated ERK1,2 phosphorylation in cultured cortical neurons and choroid plexus epithelial cells that endogenously express 5-HT(2C) receptors. Collectively, these findings demonstrate that physical interaction of CaM with recombinant and native 5-HT(2C) receptors is critical for G protein-independent, arrestin-dependent receptor signaling. This signaling pathway might be involved in neurogenesis induced by chronic treatment with 5-HT(2C) receptor agonists and their antidepressant-like activity.
File Format	PDF HTM / HTML
DOI	10.1091/mbc.E08-04-0422
Alternate Webpage(s)	http://www.molbiolcell.org/content/19/11/4640.full.pdf
Alternate Webpage(s)	http://citeseerx.ist.psu.edu/viewdoc/download;jsessionid=4AC7F49B8F73480681ADAC8ECE3018BB?doi=10.1.1.323.3068&rep=rep1&type=pdf
PubMed reference number	18768750
Alternate Webpage(s)	https://doi.org/10.1091/mbc.E08-04-0422
Journal	Medline
Volume Number	19
Issue Number	11
Journal	Molecular biology of the cell
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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