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 maintenance of muscle integrity during the mechanical stresses of contraction and relaxation. In addition to providing a membrane scaffold, members of the DPC such as the alpha-dystrobrevin protein family are thought to play an important role in intracellular signal transduction. To gain additional insights 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 evolutionary conserved 40-kDa coiled-coil-containing protein that binds to alpha- and beta-dystrobrevin in muscle and brain. Dystrophin and alpha-dystrobrevin are co-immunoprecipitated with dysbindin, indicating that dysbindin is DPC-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 certain axon terminals, notably mossy fiber synaptic terminals in the cerebellum and hippocampus. These findings have implications for the molecular pathology of Duchenne muscular dystrophy and may provide an alternative route for anchoring dystrobrevin and the DPC to the muscle membrane.
Benson
M A
MA
Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, United Kingdom.
Newey
S E
SE
Martin-Rendon
E
E
Hawkes
R
R
Blake
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D000074765:Dysbindin; D016189:Dystrophin / Q000235:genetics; D049029:Dystrophin-Associated Proteins; D005455:Fluorescent Antibody Technique; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018101:Mice, Inbred mdx; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques; D015003:Yeasts / Q000235:genetics
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C498992:Dtnbp1 protein, mouse; D000074765:Dysbindin; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C098885:dystrobrevin