The dystroglycan complex is necessary for stabilization of acetylcholine receptor clusters at neuromuscular junctions and formation of the synaptic basement membrane
Date
2001-02
Authors
Jacobson, C.
Cote, Patrice D.
Rossi, SG
Rotundo, RL
Carbonetto, S.
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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 acetyl choline 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.
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Citation
Jacobson, C., PD Cote, SG Rossi, RL Rotundo, et al. 2001. "The dystroglycan complex is necessary for stabilization of acetylcholine receptor
clusters at neuromuscular junctions and formation of the synaptic basement membrane." Journal of Cell Biology 152(3): 435-450.