Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain

The dystrophin-associated protein complex (DPC) is required for the mainten ance of muscle integrity during the mechanical stresses of contraction and relaxation. In addition to providing a membrane scaffold, members of the DP C such as the alpha -dystrobrevin protein family are thought to play an imp ortant role in intracellular signal transduction. To gain additional insigh ts into the function of the DPC, we performed a yeast two-hybrid screen for dystrobrevin-interacting proteins. Here we describe the identification of a dysbindin, a novel dystrobrevin-binding protein. Dysbindin is an evolutio nary conserved 40-kDa coiled-coil-containing protein that binds to alpha- a nd beta -dystrobrevin in muscle and brain. Dystrophin and alpha -dystrobrev in are co-immunoprecipitated with dysbindin, indicating that dysbindin is D PC-associated in muscle. Dysbindin co-localizes with alpha -dystrobrevin at the sarcolemma and is up-regulated in dystrophin-deficient muscle. In the brain, dysbindin is found primarily in axon bundles and especially in certa in axon terminals, notably messy fiber synaptic terminals in the cerebellum and hippocampus. These findings have implications for the molecular pathol ogy of Duchenne muscular dystrophy and may provide an alternative route for anchoring dystrobrevin and the DPC to the muscle membrane.