DISTRIBUTION OF ALPHA-DYSTROGLYCAN DURING EMBRYONIC NERVE-MUSCLE SYNAPTOGENESIS

The distribution of alpha-dystroglycan (alpha DG) relative to acetylch oline receptors (AChRs) and neural agrin was examined by immunofluores cent staining with mAb IIH6 in cultures of nerve and muscle cells deri ved from Xenopus embryos. In Western blots probed with mAb IIH6, alpha DG was evident in membrane extracts of Xenopus muscle but not brain. alpha DG immunofluorescence was present at virtually all synaptic clus ters of AChRs and neural agrin. Even microclusters of AChRs and agrin at synapses no older than 1-2 h (the earliest examined) had alpha DG a ssociated with them. alpha DG was also colocalized at the submicromete r level with AChRs at nonsynaptic clusters that have little or no agri n. The number of large (>4 mu m) nonsynaptic clusters of alpha DG, lik e the number of large nonsynaptic clusters of AChRs, was much lower on innervated than on noninnervated cells. When mAb IIH6 was included in the culture medium, the large nonsynaptic clusters appeared fragmente d and less compact, but the accumulation of agrin and AChRs along nerv e-muscle contacts was not prevented. It is concluded that during nerve -muscle synaptogenesis, alpha DG undergoes the same nerve-induced chan ges in distribution as AChRs. We propose a diffusion trap model in whi ch the alpha DG-transmembrane complex participates in the anchoring an d recruitment of AChRs and alpha DG during the formation of synaptic a s well as nonsynaptic AChR clusters.