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SAM68 regulates neuronal activity-dependent alternative splicing of Neurexin-1

Iijima, Takatoshi and Wu, Karen and Witte, Harald and Hanno-Iijima, Yoko and Glatter, Timo and Richard, Stéphane and Scheiffele, Peter. (2011) SAM68 regulates neuronal activity-dependent alternative splicing of Neurexin-1. Cell, Vol. 147, H. 7. S. 1601-1614.

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Official URL: http://edoc.unibas.ch/dok/A5849132

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Abstract

The assembly of synapses and neuronal circuits relies on an array of molecular recognition events and their modification by neuronal activity. Neurexins are a highly polymorphic family of synaptic receptors diversified by extensive alternative splicing. Neurexin variants exhibit distinct isoform-specific biochemical interactions and synapse assembly functions, but the mechanisms governing splice isoform choice are not understood. We demonstrate that Nrxn1 alternative splicing is temporally and spatially controlled in the mouse brain. Neuronal activity triggers a shift in Nrxn1 splice isoform choice via calcium/calmodulin-dependent kinase IV signaling. Activity-dependent alternative splicing of Nrxn1 requires the KH-domain RNA-binding protein SAM68 that associates with RNA response elements in the Nrxn1 pre-mRNA. Our findings uncover SAM68 as a key regulator of dynamic control of Nrxn1 molecular diversity and activity-dependent alternative splicing in the central nervous system.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Scheiffele)
05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Proteomics (Schmidt)
UniBasel Contributors:Scheiffele, Peter and Glatter, Timo
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cell Press
ISSN:0092-8674
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:11
Deposited On:14 Sep 2012 06:41

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