Dystroglycan contributes to the formation of multiple dystrophin-like complexes in brain

In muscle, dystrophin anchors a complex of proteins at the cell surface whi ch Includes alpha -dystroglycan, beta -dystroglycan, syntrophins and dystro brevins. Mutations in the dystrophin gene lead to muscular dystrophy and me ntal retardation. In contrast to muscle, little is known about the localiza tion and the molecular interactions of dystrophin and dystrophin associated proteins (DAPs) in brain. In the present study, we show that alpha -dystro glycan and dystrophin are localized to large neurones in cerebral cortex, h ippocampus, cerebellum and spinal cord. Furthermore, we show that dystrogly can is a member of three distinct dystrophin-containing complexes. Two of t hese complexes contain syntrophin and both dystrophin and syntrophin are en riched in post-synaptic densities. These data suggest that dystrophin and D APs may have a role in the organization of CNS synapses, Interestingly, the enrichment for syntrophin in post-synaptic densities is not affected in mi ce mutant for all dystrophin isoforms. Thus in the brain, unlike in muscle, the association of syntrophin with dystrophin is not crucial for the DAP c omplex which suggests that it may be associated with other proteins.