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

Benson, Matthew A., Newey, Sarah E., Martin-Rendon, Enca, Hawkes, Richard and Blake, Derek J. ORCID: https://orcid.org/0000-0002-5005-4731 2001. Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain. Journal of Biological Chemistry 276 (26) , pp. 24232-24241. 10.1074/jbc.M010418200

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Abstract

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 α-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 α- and β-dystrobrevin in muscle and brain. Dystrophin and α-dystrobrevin are co-immunoprecipitated with dysbindin, indicating that dysbindin is DPC-associated in muscle. Dysbindin co-localizes with α-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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Mathematics Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	R Medicine > R Medicine (General)
Publisher:	American Society for Biochemistry and Molecular Biology
ISSN:	0021-9258
Last Modified:	24 Oct 2022 11:46
URI:	https://orca.cardiff.ac.uk/id/eprint/49255

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