β-Dystrobrevin, a New Member of the Dystrophin Family
IDENTIFICATION, CLONING, AND PROTEIN ASSOCIATIONS*
- Matthew F. Peters‡,
- Kristine F. O’Brien§,
- Hélène M. Sadoulet-Puccio§,
- Louis M. Kunkel§¶,
- Marvin E. Adams‡ and
- Stanley C. Froehner‡‖
- From the ‡Department of Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7545 and §Howard Hughes Medical Institute, Division of Genetics, The Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115
Abstract
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.
Footnotes
-
↵* This study was supported in part by National Institutes of Health Grants NS33145 (to S. C. F. and R. Sealock), NS14871 (to S. C. F.), NS23740-09 (to L. M. K.), and a Muscular Dystrophy Association Grant (to S. C. F.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵¶ An Investigator of the Howard Hughes Medical Institute.
-
↵‖ To whom correspondence should be addressed: Tel.: 919-966-1239; Fax: 919-966-6413; E-mail: froehner{at}med.unc.edu.
-
↵1 The abbreviations used are: CR, cysteine-rich; CT, carboxyl-terminal; Ab, polyclonal antibody; CRCT, cysteine-rich COOH-terminal region of dystrophin; DAP, dystrophin-associated protein; DRP, dystrophin-related protein; DUR, dystrobrevin-unique region; EST, expressed sequence tag; mAb, monoclonal antibody; contig, group of overlapping clones; kb, kilobases; vr, variable regions.
-
↵2 Sadoulet-Puccio, H. M., Rajala, M. and Kunkel, L. M., Proc. Natl. Acad. Sci., in press.
-
- Received September 15, 1997.
- Revision received October 6, 1997.
