Research article summary (published 3 Feb 2001):

The dystroglycan complex is necessary for stabilization of acetylcholine receptor clusters at neuromuscular junctions and formation of the synaptic basement membrane.

Full Abstract

The dystrophin-associated protein (DAP) complex spans the sarcolemmal membrane linking the cytoskeleton to the basement membrane surrounding each myofiber. Defects in the DAP complex have been linked previously to a variety of muscular dystrophies. Other evidence points to a role for the DAP complex in formation of nerve-muscle synapses. We show that myotubes differentiated from dystroglycan-/- embryonic stem cells are responsive to agrin, but produce acetylcholine receptor (AChR) clusters which are two to three times larger in area, about half as dense, and significantly less stable than those on dystroglycan+/+ myotubes. AChRs at neuromuscular junctions are similarly affected in dystroglycan-deficient chimeric mice and there is a coordinate increase in nerve terminal size at these junctions. In culture and in vivo the absence of dystroglycan disrupts the localization to AChR clusters of laminin, perlecan, and acetylcholinesterase (AChE), but not rapsyn or agrin. Treatment of myotubes in culture with laminin induces AChR clusters on dystroglycan+/+, but not -/- myotubes. These results suggest that dystroglycan is essential for the assembly of a synaptic basement membrane, most notably by localizing AChE through its binding to perlecan. In addition, they suggest that dystroglycan functions in the organization and stabilization of AChR clusters, which appear to be mediated through its binding of laminin.

Author information

Author/s: Jacobson, C (C); Côté, P D (PD); Rossi, S G (SG); Rotundo, R L (RL); Carbonetto, S (S);

Affiliation: Department of Biology, McGill University/Center for Neuroscience Research, Montréal General Hospital Research Institute, Montréal, Québec H3G 1A4, Canada.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

Journal: The Journal of cell biology (J Cell Biol), published in United States. (Language: eng)

Reference: 2001-Feb; vol 152 (issue 3) : pp 435-50

Dates: Created 2001/02/22; Completed 2001/05/24; Revised 2008/11/20;

PMID: 11157973, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Agrin - metabolism Animals Basement Membrane - chemistry; metabolism Cell Line Cells, Cultured Chimera Collagen - metabolism Cytoskeletal Proteins - genetics; metabolism Dystroglycans Dystrophin Fibronectins - metabolism Heparan Sulfate Proteoglycans - metabolism

Laminin - metabolism Membrane Glycoproteins - genetics; metabolism Mice Microscopy, Fluorescence Models, Biological Muscle Development Muscle Proteins - metabolism Muscle, Skeletal - anatomy & histology; growth & development; physiology Neuromuscular Junction - chemistry; physiology Receptors, Cholinergic - metabolism Stem Cells - metabolism Synaptophysin - metabolism

Associated Chemicals: Agrin (0) ; Cytoskeletal Proteins (0) ; Dystrophin (0) ; Fibronectins (0) ; Heparan Sulfate Proteoglycans (0) ; Laminin (0) ; Membrane Glycoproteins (0) ; Muscle Proteins (0) ; Receptors, Cholinergic (0) ; Synaptophysin (0) ; peripheral membrane protein 43K (0) ; perlecan (143972-95-6) ; Dystroglycans (146888-27-9) ; Collagen (9007-34-5)

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