DYSTROGLYCAN BINDS NERVE AND MUSCLE AGRIN

Neurally released agrin is thought to cluster acetylcholine receptors (AChRs) and other synaptic proteins in the postsynaptic membrane durin g synaptogenesis at the neuromuscular junction. We have examined the b inding of nerve and muscle agrins, which have dramatically different a bilities to cluster AChRs, to the membrane proteins of Torpedo electri c organ and C2 myotubes. Both bound with approximately nanomolar affin ity to a single component identified as alpha-dystroglycan: agrin bind ing was blocked by antibodies to alpha-dystroglycan, and agrin bound t o purified alpha-dystroglycan. Dystroglycan was altered in two genetic variants of C2 muscle cells that fail to form spontaneous clusters of AChRs and that show a diminished response to agrin. Antibodies that b locked alpha-dystroglycan binding, however, failed to block the cluste ring of AChRs by neural agrin. Although alpha-dystroglycan is the majo r agrin-binding protein in Torpedo and myotube membranes, its physiolo gical role is unclear.