Formation of the neuromuscular junction (NMJ) requires interaction between specific extracellular matrix proteins, intracellular cytoskeletal elements, and clustering of specific neurotransmitter receptors. Dystroglycans, α-dystroglycan and β-dystroglycan, are two members of the dystrophin-associated complex, an essential element of NMJs. These proteins are encoded by the same gene, but posttranslationally cleaved to produce a 156 kDa extracellular peripheral membrane protein, α-dystroglycan, and a 43 kDa transmembrane protein, β-dystroglycan. Dystroglycans are expressed highest in heart and muscle, but are also found in non-muscle tissues. α-dystroglycan may interact with agrin to facilitate AChR clustering at NMJs, and has been implicated as a laminin receptor. β-dystroglycan recruits dystrophin to the sarcolemma, and interactions between β-dystroglycan and caveolin-3 may regulate this recruitment. Mice deficient in dystroglycans have severly disorganized NMJs, and have reductions in the concentration of laminin, perlecan, and AChE at the synaptic basement membrane of NMJs. Thus, dystroglycans may have important extracellular and intracellular roles during NMJ assembly.
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