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

217Citations
Citations of this article
294Readers
Mendeley users who have this article in their library.

This article is free to access.

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. © 2011 Elsevier Inc.

Cite

CITATION STYLE

APA

Iijima, T., Wu, K., Witte, H., Hanno-Iijima, Y., Glatter, T., Richard, S., & Scheiffele, P. (2011). SAM68 regulates neuronal activity-dependent alternative splicing of neurexin-1. Cell, 147(7), 1601–1614. https://doi.org/10.1016/j.cell.2011.11.028

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free