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Originally published In Press as doi:10.1074/jbc.M600912200 on March 10, 2006
J. Biol. Chem., Vol. 281, Issue 19, 13365-13373, May 12, 2006
An Extracellular Pathway for Dystroglycan Function in Acetylcholine Receptor Aggregation and Laminin Deposition in Skeletal Myotubes*
Mathieu R. Tremblay and
Salvatore Carbonetto 1
From the
Department of Biology, Center for Research in Neuroscience, McGill University, Montréal General Hospital Research Institute, Montréal, Québec H3G 1A4, Canada
The dystroglycan (DG) complex is involved in agrin-induced acetylcholine receptor clustering downstream of muscle-specific kinase where it regulates the stability of acetylcholine receptor aggregates as well as assembly of the synaptic basement membrane. We have previously proposed that this entails coordinate extracellular and intracellular interactions of its two subunits, - and -DG. To assess the contribution of the extracellular and intracellular portions of DG, we have used adenoviruses to express full-length and deletion mutants of -DG in myotubes derived from wild-type embryonic stem cells or from cells null for DG. We show that -DG is properly glycosylated and targeted to the myotube surface in the absence of -DG. Extracellular interactions of DG modulate the size and the microcluster density of agrin-induced acetylcholine receptor aggregates and are responsible for targeting laminin to these clusters. Thus, the association of - and -DG in skeletal muscle may coordinate independent roles in signaling. We discuss how DG may regulate synapses through extracellular signaling functions of its subunit.
Received for publication, January 30, 2006
, and in revised form, March 7, 2006.
* This work was supported by a doctoral research award from Canadian Institutes of Health Research (to M. R. T.) and by grants from the Canadian Institutes of Health Research and the United States Muscular Dystrophy Association (to S. C.). 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.
1 To whom correspondence should be addressed: Center for Research in Neuroscience, McGill University, Montréal General Hospital Research Institute, 1650 Cedar, Montréal, Québec, Canada, H3G 1A4. Tel.: 514-934-1934, ext. 44237; Fax: 514-934-8265; E-mail: Sal.carbonetto{at}mcgill.ca.

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Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.
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