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

J. Biol. Chem., Vol. 278, Issue 45, 44868-44873, November 7, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/45/44868    most recent M307026200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McDearmon, E. L. Articles by Ervasti, J. M. Search for Related Content PubMed PubMed Citation Articles by McDearmon, E. L. Articles by Ervasti, J. M. Social Bookmarking                      What's this?

Core 1 Glycans on -Dystroglycan Mediate Laminin-induced Acetylcholine Receptor Clustering but Not Laminin Binding^*

Erin L. McDearmon, Ariana C. Combs, and James M. Ervasti¶

From the Graduate Program in Molecular and Cellular Pharmacology and the Department of Physiology, University of Wisconsin-Madison Medical School, Madison, Wisconsin 53706

Although unique O-linked oligosaccharides on -dystroglycan are important for binding to a variety of extracellular ligands, the function(s) of more generic carbohydrate structures on -dystroglycan remain unclear. Recent studies suggest a role for glycoconjugates bearing the core 1 disaccharide Gal(1–3)GalNAc in acetylcholine receptor (AChR) clustering on the surface of muscle cells. Here, we report experiments demonstrating that the core 1-specific lectin jacalin almost completely abrogated laminin-induced AChR clustering in C2C12 myotubes and that -dystroglycan was the predominant jacalin-binding protein detected in C2C12 myotube lysates. Although jacalin likely inhibited laminin-induced AChR clustering by directly binding to -dystroglycan, jacalin had no effect on laminin binding to the myotube surface or to -dystroglycan. Like jacalin, peanut agglutinin lectin also binds the core 1 disaccharide but not when it is terminally sialylated as expressed on -dystroglycan. We show that C2C12 -dystroglycan bound to peanut agglutinin only after digestion with neuraminidase. Simultaneous treatment of myotubes with neuraminidase and endo-O-glycosidase diminished -dystroglycan binding to peanut agglutinin and inhibited neuraminidase-induced AChR clustering. We conclude that sialylated core 1 oligosaccharides of -dystroglycan are important for laminin-induced AChR clustering and that their function in this process is distinct from the established role of -dystroglycan oligosaccharides in laminin binding.

Received for publication, July 1, 2003 , and in revised form, August 15, 2003.

^* This work was supported by the Muscular Dystrophy Association and National Institutes of Health Grant ARO1985 (to J. M. E.) and an American Heart Association-Northland Affiliate Pre-Doctoral Fellowship (to E. L. M.). 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.

^¶ To whom correspondence should be addressed: Dept. of Physiology, University of Wisconsin-Madison, 127 Service Memorial Institute, 1300 University Ave., Madison, WI 53706. Tel.: 608-265-3419; Fax: 608-265-5512; E-mail: ervasti{at}physiology.wisc.edu.

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

This article has been cited by other articles:

				J. M. Rojek, C. F. Spiropoulou, K. P. Campbell, and S. Kunz Old World and Clade C New World Arenaviruses Mimic the Molecular Mechanism of Receptor Recognition Used by {alpha}-Dystroglycan's Host-Derived Ligands J. Virol., June 1, 2007; 81(11): 5685 - 5695. [Abstract] [Full Text] [PDF]

				D. Harrison, S.-A. Hussain, A. C. Combs, J. M. Ervasti, P. D. Yurchenco, and E. Hohenester Crystal Structure and Cell Surface Anchorage Sites of Laminin {alpha}1LG4-5 J. Biol. Chem., April 13, 2007; 282(15): 11573 - 11581. [Abstract] [Full Text] [PDF]

				M. R. Tremblay and S. Carbonetto An Extracellular Pathway for Dystroglycan Function in Acetylcholine Receptor Aggregation and Laminin Deposition in Skeletal Myotubes J. Biol. Chem., May 12, 2006; 281(19): 13365 - 13373. [Abstract] [Full Text] [PDF]

				S. K. Patnaik and P. Stanley Mouse Large Can Modify Complex N- and Mucin O-Glycans on {alpha}-Dystroglycan to Induce Laminin Binding J. Biol. Chem., May 27, 2005; 280(21): 20851 - 20859. [Abstract] [Full Text] [PDF]

				J. C. Trinidad and J. B. Cohen Neuregulin Inhibits Acetylcholine Receptor Aggregation in Myotubes J. Biol. Chem., July 23, 2004; 279(30): 31622 - 31628. [Abstract] [Full Text] [PDF]