| First Author | Adams ME | Year | 2008 |
| Journal | J Cell Sci | Volume | 121 |
| Issue | Pt 1 | Pages | 48-54 |
| PubMed ID | 18057022 | Mgi Jnum | J:130745 |
| Mgi Id | MGI:3772283 | Doi | 10.1242/jcs.020701 |
| Citation | Adams ME, et al. (2008) Differential targeting of nNOS and AQP4 to dystrophin-deficient sarcolemma by membrane-directed {alpha}-dystrobrevin. J Cell Sci 121(Pt 1):48-54 |
| abstractText | alpha-Dystrobrevin associates with and is a homologue of dystrophin, the protein linked to Duchenne and Becker muscular dystrophies. We used a transgenic approach to restore alpha-dystrobrevin to the sarcolemma in mice that lack dystrophin (mdx mice) to study two interrelated functions: (1) the ability of alpha-dystrobrevin to rescue components of the dystrophin complex in the absence of dystrophin and (2) the ability of sarcolemmal alpha-dystrobrevin to ameliorate the dystrophic phenotype. We generated transgenic mice expressing alpha-dystrobrevin-2a linked to a palmitoylation signal sequence and bred them onto the alpha-dystrobrevin-null and mdx backgrounds. Expression of palmitoylated alpha-dystrobrevin prevented the muscular dystrophy observed in the alpha-dystrobrevin-null mice, demonstrating that the altered form of alpha-dystrobrevin was functional. On the mdx background, the palmitoylated form of alpha-dystrobrevin was expressed on the sarcolemma but did not significantly ameliorate the muscular dystrophy phenotype. Palmitoylated dystrobrevin restored alpha-syntrophin and aquaporin-4 (AQP4) to the mdx sarcolemma but was unable to recruit beta-dystroglycan or the sarcoglycans. Despite restoration of sarcolemmal alpha-syntrophin, neuronal nitric oxide synthase (nNOS) was not localized to the sarcolemma, suggesting that nNOS requires both dystrophin and alpha-syntrophin for correct localization. Thus, although nNOS and AQP4 both require interaction with the PDZ domain of alpha-syntrophin for sarcolemmal association, their localization is regulated differentially. |
