A novel mechanism for modulating synaptic gene expression: Differential localization of alpha-dystrobrevin transcripts in skeletal muscle

alpha -Dystrobrevin is a dystrophin-related and -associated protein that is involved in synapse maturation and is required for normal muscle function. There are three protein isoforms in skeletal muscle, alpha -dystrobrevin-1 , -2, and -3 that are encoded by the single alpha -dystrobrevin gene. To un derstand the role of these proteins in muscle we have investigated the loca lisation and transcript distribution of the different alpha -dystrobrevin i soforms. alpha -Dystrobrevin-1 and -2 are concentrated at the neuromuscular junction and are both recruited into agrin-induced acetylcholine receptor clusters in cultured myotubes. We also demonstrate that all a-dystrobrevin mRNAs are transcribed from a single promoter in skeletal muscle. However, o nly transcripts encoding alpha -dystrobrevin-1 are preferentially accumulat ed at postsynaptic sites. These data suggest that the synaptic accumulation of alpha -dystrobrevin-1 mRNA occurs posttranscriptionally, identifying a novel mechanism for synaptic gene expression. Taken together, these results indicate that different isoforms possess distinct roles in synapse formati on and possibly in the pathogenesis of muscular dystrophy.