期刊
FASEB JOURNAL
卷 20, 期 10, 页码 1724-+出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.05-5124fje
关键词
dystrophin-associated protein complex; alpha-dystrobrevin-2; sarcoglycans; beta 1-syntrophin
资金
- NCRR NIH HHS [RR15578, P20 RR015578] Funding Source: Medline
- NIAMS NIH HHS [AR42826, R01 AR042826] Funding Source: Medline
- NICHD NIH HHS [HD23924, R01 HD023924-14S1, R01 HD023924-16, R01 HD023924-12, R01 HD023924-15, R01 HD023924-17, R01 HD023924-13A1, R01 HD023924-14, R01 HD023924] Funding Source: Medline
- NIMH NIH HHS [T32 MH020068, T32 MH020068-03, T32 MH020068-05, T32 MH020068-01, T32 MH020068-04, T32 MH020068-02, T32MH20068] Funding Source: Medline
- NINDS NIH HHS [R01 NS033145, NS4678, R44 NS045432, NS33145] Funding Source: Medline
The dystrophin-associated protein complex (DAPC) provides a linkage between the cytoskeleton and the extracellular matrix (ECM) and is also a scaffold for a host of signaling molecules. The constituents of the DAPC must be targeted to the sarcolemma in order to properly function. Biglycan is an ECM molecule that associates with the DAPC. Here, we show that biglycan null mice exhibit a mild dystrophic phenotype and display a selective reduction in the localization of alpha-dystrobrevin-1 and -2, alpha- and beta 1-syntrophin, and nNOS at the sarcolemma. Purified biglycan induces nNOS redistribution to the plasma membrane in cultured muscle cells. Biglycan protein injected into muscle becomes stably associated with the sarcolemma and ECM for at least 2 wk. This injected biglycan restores the sarcolemmal expression of alpha-dystrobrevin-1 and -2, and beta 1- and beta 2-syntrophin in biglycan null mice. We conclude that biglycan is important for the maintenance of muscle cell integrity and plays a direct role in regulating the expression and sarcolemmal localization of the intracellular signaling proteins dystrobrevin-1 and -2, alpha- and beta 1-syntrophin and nNOS.
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