QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 24 October 2007
doi: 10.1242/dev.010702

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.010702v1 134/23/4167    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Friese, M. B. Articles by Burden, S. J. Search for Related Content PubMed PubMed Citation Articles by Friese, M. B. Articles by Burden, S. J.

Synaptic differentiation is defective in mice lacking acetylcholine receptor ß-subunit tyrosine phosphorylation

Molecular Neurobiology Program, The Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, NYU Medical School, 540 First Avenue, New York, NY 10016, USA.

^* Author for correspondence (e-mail: burden{at}saturn.med.nyu.edu)

Accepted 11 September 2007

Agrin activates MuSK, a receptor tyrosine kinase expressed in skeletal muscle, leading to tyrosine phosphorylation of the acetylcholine receptor (AChR) ß-subunit and clustering of AChRs. The importance of AChR ß-subunit tyrosine phosphorylation in clustering AChRs and regulating synaptic differentiation is poorly understood. We generated mice with targeted mutations in the three intracellular tyrosines of the AChR ß-subunit (AChR-ß^3F/3F). Mice lacking AChR ß-subunit tyrosine phosphorylation thrive postnatally and have no overt behavioral defects, indicating that AChR ß-subunit tyrosine phosphorylation is not essential for the formation of neuromuscular synapses. Nonetheless, the size of synapses and the density of synaptic AChRs are reduced in AChR- ß^3F/3F mutant mice. Moreover, synapses are structurally simplified and the organization of postjunctional folds is aberrant in mice lacking tyrosine phosphorylation of the AChR ß-subunit. Furthermore, mutant AChRs cluster poorly in response to agrin and are readily extracted from the cell surface of cultured myotubes by non-ionic detergent. These data indicate that tyrosine phosphorylation of the AChR ß-subunit has an important role in organizing AChRs and regulating synaptic differentiation.

Key words: AChR clustering, Junctional folds, Neuromuscular junction, Synaptogenesis, Chrnb1