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The Journal of Neuroscience, June 1, 2002, 22(11):4274-4285
Dystroglycan Is Selectively Associated with Inhibitory GABAergic
Synapses But Is Dispensable for Their Differentiation
Sabine
Lévi1,
R.
Mark
Grady1,
Michael D.
Henry2,
Kevin P.
Campbell2,
Joshua R.
Sanes1, and
Ann Marie
Craig1
1 Washington University, Department of Anatomy and
Neurobiology, St. Louis, Missouri 63110, and 2 Howard
Hughes Medical Institute, Departments of Physiology and Biophysics and
of Neurology, University of Iowa College of Medicine, Iowa City, Iowa
52242
The dystrophin glycoprotein complex (DGC) is a multimolecular
complex that links the extracellular matrix to the cytoskeleton. The
DGC is present at the skeletal neuromuscular junction and required for
its maturation and maintenance. Members of the DGC are also expressed
in brain. We used cultured hippocampal neurons to analyze the
distribution, regulation, and role in synaptogenesis of the major
transmembrane component of the DGC, dystroglycan; one of its
extracellular ligands, agrin; and one of its cytoskeletal binding
partners, dystrophin.  -Dystroglycan,  -dystroglycan, and
dystrophin clustered at a subset of inhibitory synapses containing GABAAR subunits 1, 2, and  2, and the inhibitory
receptor anchoring protein gephyrin. DGC components were not detected
at excitatory glutamatergic synapses. Dystroglycan is the first
identified adhesive macromolecule at mature GABA synapses.
Developmentally, dystroglycan clustered at synaptic loci after synaptic
vesicles, GABAAR, and gephyrin, the latter being closely
associated with GABAAR at all stages of synaptogenesis
analyzed. Analysis of gephyrin  /, agrin /, and
mdx mouse hippocampal neurons in culture indicated that synaptic clustering of dystroglycan occurs independently of gephyrin, agrin, and dystrophin. In dystroglycan-deficient neurons, cultured from
a conditional mutant strain, GABAergic synapses differentiated with
clusters of gephyrin and GABAAR apposed to synaptic
terminals, but these synapses did not contain detectable dystrophin.
Thus the DGC is not essential for GABAergic synaptogenesis but is
likely to function in modulating inhibitory synapses or conferring
specialized properties on a subset of them.
Key words:
synaptogenesis; GABA receptor; gephyrin; dystrophin; agrin; mdx
Copyright © 2002 Society for Neuroscience 0270-6474/02/22114274-12$05.00/0
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