β-Dystrobrevin, a New Member of the Dystrophin Family

• Published in: The Journal of biological chemistry 1997-12, Vol.272 (50), p.31561-31569
• Main Authors: Peters, Matthew F., O'Brien, Kristine F., Sadoulet-Puccio, Hélène M., Kunkel, Louis M., Adams, Marvin E., Froehner, Stanley C.
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.272.50.31561

Dystrophin, the protein disrupted in Duchenne muscular dystrophy, is one of several related proteins that are key components of the submembrane cytoskeleton. Three dystrophin-related proteins (utrophin, dystrophin-related protein-2 (DRP2), and dystrobrevin) have been described. Here, we identify a human gene on chromosome 2p22–23 that encodes a novel protein, β-dystrobrevin, with significant homology to the other known dystrobrevin (now termed α-dystrobrevin). Sequence alignments including this second dystrobrevin strongly support the concept that two distinct subfamilies exist within the dystrophin family, one composed of dystrophin, utrophin, and DRP2 and the other composed of α- and β-dystrobrevin. The possibility that members of each subfamily form distinct protein complexes was examined by immunopurifying dystrobrevins and dystrophin. A β-dystrobrevin antibody recognized a protein of the predicted size (71 kDa) that copurified with the dystrophin short form, Dp71. Thus, like α-dystrobrevin, β-dystrobrevin is likely to associate directly with dystrophin. α- and β-dystrobrevins failed to copurify with each other, however. These results suggest that members of the dystrobrevin subfamily form heterotypic associations with dystrophin and raise the possibility that pairing of a particular dystrobrevin with dystrophin may be regulated, thereby providing a mechanism for assembly of distinct submembrane protein complexes.