Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Alternative splicing of dystrobrevin regulates the stoichiometry of syntrophin binding to the dystrophin protein complex

Newey, Sarah E., Benson, Matthew A., Ponting, Chris P., Davies, Kay E. and Blake, Derek J. 2000. Alternative splicing of dystrobrevin regulates the stoichiometry of syntrophin binding to the dystrophin protein complex. Current Biology 10 (20) , pp. 1295-1298. 10.1016/S0960-9822(00)00760-0

Full text not available from this repository.

Abstract

Dystrophin coordinates the assembly of a complex of structural and signalling proteins that is required for normal muscle function. A key component of the dystrophin-associated protein complex (DPC) is ?-dystrobrevin, a dystrophin-related and -associated protein whose absence results in muscular dystrophy and neuromuscular junction defects. The current model of the DPC predicts that dystrophin and dystrobrevin each bind a single syntrophin molecule. The syntrophins are PDZ-domain-containing proteins that facilitate the recruitment of signalling proteins such as nNOS (neuronal nitric oxide synthase) to the DPC. Here we show, using yeast two-hybrid analysis and biochemical binding studies, that ?-dystrobrevin in fact contains two independent syntrophin-binding sites in tandem. The previously undescribed binding site is situated within an alternatively spliced exon of ?-dystrobrevin, termed the variable region-3 (vr3) sequence, which is specifically expressed in skeletal and cardiac muscle. Analysis of the syntrophin-binding region of dystrobrevin reveals a tandem pair of predicted ? helices with significant sequence similarity. These ? helices, each termed a syntrophin-binding motif, are also highly conserved in dystrophin and utrophin. Together these data show that there are four potential syntrophin-binding sites per dystrophin complex in skeletal muscle: two on dystrobrevin and two on dystrophin or utrophin. Furthermore, alternative splicing of dystrobrevin provides a mechanism for regulating the stoichiometry of syntrophin association with the DPC. This is likely to have important consequences for the recruitment of specific signalling molecules to the DPC and ultimately for its function.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Publisher: Cell Press
ISSN: 0960-9822
Last Modified: 04 Jun 2017 05:11
URI: http://orca-mwe.cf.ac.uk/id/eprint/49259

Citation Data

Cited 77 times in Google Scholar. View in Google Scholar

Cited 73 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item