Maturation and maintenance of the neuromuscular synapse: Genetic evidence for roles of the dystrophin-glycoprotein complex

The dystrophin-glycoprotein complex (DGC) links the cytoskeleton of muscle fibers to their extracellular matrix. Using knockout mice, we show that a c ytoplasmic DGC component, alpha-dystrobrevin (alpha-DB), is dispensable for formation of the neuromuscular junction (NMJ) but required for maturation of its postsynaptic apparatus. We also analyzed double and triple mutants l acking other cytoskeletal DGC components (utrophin and dystrophin) and myot ubes lacking a alpha-DB or a transmembrane DGC component (dystroglycan). Ou r results suggest that alpha-DB acts via its linkage to the DGC to enhance the stability of postsynaptic specializations following their DGC-independe nt formation; dystroglycan may play additional roles in assembling synaptic basal lamina. Together, these results demonstrate involvement of distinct protein complexes in the formation and maintenance of the synapse and impli cate the DGC in the latter process.