| Abstract | Dystrobrevin is one of the intracellular components of the transmembrane dystrophin-glycoprotein complex (DGC). The functional role of this complex in normal and pathological situations has not yet been clearly established. Dystrobrevin disappears from the muscle membrane in Duchenne muscular dystrophy (DMD), which results from dystrophin mutations, as well as in limb girdle muscular dystrophies (LGMD), which results from mutations affecting other members of the DGC complex. These findings therefore suggest that dystrobrevin may play a pivotal role in the progression of these clinically related diseases. In this study, we used the Caenorhabditis elegans model to address the question of the relationship between dystrobrevin binding to dystrophin and dystrobrevin function. Deletions of the dystrobrevin protein were performed and the ability of the mutated forms to bind to dystrophin was tested both in vitro and in a two-hybrid assay, as well as their ability to rescue dystrobrevin (dyb-1) mutations in C. elegans. The deletions affecting the second helix of the Dyb-1 coiled-coil domain abolished the binding of dystrobrevin to dystrophin both in vitro and in the two-hybrid assay. These deletions also abolished the rescuing activity of a functional transgene in vivo. These results are consistent with a model according to which dystrobrevin must bind to dystrophin to be able to function properly. |
| Authors | Karine Grisoni, Kathrin Gieseler, Laurent Ségalat
(Affiliation: CGMC, CNRS-UMR, Université Lyon, Villeurbanne, France.)
|
| Journal | European journal of biochemistry / FEBS
(Eur J Biochem)
Vol. 269
Issue 6
Pg. 1607-12
(Mar 2002)
ISSN: 0014-2956 Germany |
| PMID | 11895430
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Cytoskeletal Proteins
- Dystrophin
- Dystrophin-Associated Proteins
- Membrane Proteins
- dystrobrevin
|
| Topics |
- Animals
- Binding Sites
- Caenorhabditis elegans
(genetics, metabolism)
- Cytoskeletal Proteins
(chemistry, metabolism)
- Dystrophin
(metabolism)
- Dystrophin-Associated Proteins
- Genetic Complementation Test
- Membrane Proteins
(chemistry, metabolism)
- Mutagenesis
- Two-Hybrid System Techniques
|
