HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 30, 31622-31628, July 23, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/30/31622    most recent M400044200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Trinidad, J. C. Articles by Cohen, J. B. Search for Related Content PubMed PubMed Citation Articles by Trinidad, J. C. Articles by Cohen, J. B. Social Bookmarking                      What's this?

Neuregulin Inhibits Acetylcholine Receptor Aggregation in Myotubes^*

Jonathan C. Trinidad and Jonathan B. Cohen

From the Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115

The high local concentration of acetylcholine receptors (AChRs) at the vertebrate neuromuscular junction results from their aggregation by the agrin/MuSK signaling pathway and their synthetic up-regulation by the neuregulin/ErbB pathway. Here, we show a novel role for the neuregulin/ErbB pathway, the inhibition of AChR aggregation on the muscle surface. Treatment of C2C12 myotubes with the neuregulin epidermal growth factor domain decreased the number of both spontaneous and agrin-induced AChR clusters, in part by increasing the rate of cluster disassembly. Upon cluster disassembly, AChRs were internalized into caveolae (as identified by caveolin-3). Time-lapse microscopy revealed that individual AChR clusters fragmented into puncta, and application of neuregulin accelerated the rate at which AChR clusters decreased in area without affecting the density of AChRs remaining in individual clusters (as measured by the fluorescence intensity/unit area). We propose that this novel action of neuregulin regulates synaptic competition at the developing neuromuscular junction.

Received for publication, January 5, 2004 , and in revised form, May 19, 2004.

^* This work was supported in part by United States Public Health Service Grant NS18458 and a Stuart H. P. and Victoria Quan Fellowship in Neurobiology (to J. C. T.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Dept. of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143.

To whom correspondence should be addressed: Dept. of Neurobiology, Harvard Medical School, 220 Longwood Ave., Boston, MA 02115. Tel.: 617-432-1728; Fax: 617-734-7557; E-mail: jonathan_cohen{at}hms.harvard.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Kumari, V. Borroni, A. Chaudhry, B. Chanda, R. Massol, S. Mayor, and F. J. Barrantes Nicotinic acetylcholine receptor is internalized via a Rac-dependent, dynamin-independent endocytic pathway J. Cell Biol., October 22, 2008; 181(7): 1179 - 1193. [Abstract] [Full Text] [PDF]

				J. Wang, N.-J. Ruan, L. Qian, W.-l. Lei, F. Chen, and Z.-G. Luo Wnt/{beta}-Catenin Signaling Suppresses Rapsyn Expression and Inhibits Acetylcholine Receptor Clustering at the Neuromuscular Junction J. Biol. Chem., August 1, 2008; 283(31): 21668 - 21675. [Abstract] [Full Text] [PDF]

				D. Zhu, W. C. Xiong, and L. Mei Lipid rafts serve as a signaling platform for nicotinic acetylcholine receptor clustering. J. Neurosci., May 3, 2006; 26(18): 4841 - 4851. [Abstract] [Full Text] [PDF]

				A. K. Y. Fu, F. C. F. Ip, W.-Y. Fu, J. Cheung, J. H. Wang, W.-H. Yung, and N. Y. Ip Aberrant motor axon projection, acetylcholine receptor clustering, and neurotransmission in cyclin-dependent kinase 5 null mice PNAS, October 18, 2005; 102(42): 15224 - 15230. [Abstract] [Full Text] [PDF]

				P. Mittaud, A. A. Camilleri, R. Willmann, S. Erb-Vogtli, S. J. Burden, and C. Fuhrer A Single Pulse of Agrin Triggers a Pathway That Acts To Cluster Acetylcholine Receptors Mol. Cell. Biol., September 15, 2004; 24(18): 7841 - 7854. [Abstract] [Full Text] [PDF]