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Cdk5 induces constitutive activation of 5-HT6 receptors to promote neurite growth.
- Source :
- Nature Chemical Biology; Jul2014, Vol. 10 Issue 7, p590-597, 8p
- Publication Year :
- 2014
-
Abstract
- The serotonin<subscript>6</subscript> receptor (5-HT<subscript>6</subscript>R) is a promising target for treating cognitive deficits of schizophrenia often linked to alterations of neuronal development. This receptor controls neurodevelopmental processes, but the signaling mechanisms involved remain poorly understood. Using a proteomic strategy, we show that 5-HT<subscript>6</subscript>Rs constitutively interact with cyclin-dependent kinase 5 (Cdk5). Expression of 5-HT<subscript>6</subscript>Rs in NG108-15 cells induced neurite growth and expression of voltage-gated Ca<superscript>2+</superscript> channels, two hallmarks of neuronal differentiation. 5-HT<subscript>6</subscript>R-elicited neurite growth was agonist independent and prevented by the 5-HT<subscript>6</subscript>R antagonist SB258585, which behaved as an inverse agonist. Moreover, it required receptor phosphorylation at Ser350 by Cdk5 and Cdc42 activity. Supporting a role of native 5-HT<subscript>6</subscript>Rs in neuronal differentiation, neurite growth of primary neurons was reduced by SB258585, by silencing 5-HT<subscript>6</subscript>R expression or by mutating Ser350 into alanine. These results reveal a functional interplay between Cdk5 and a G protein-coupled receptor to control neuronal differentiation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15524450
- Volume :
- 10
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- Nature Chemical Biology
- Publication Type :
- Academic Journal
- Accession number :
- 96582905
- Full Text :
- https://doi.org/10.1038/nchembio.1547