title: Biglycan regulates the expression and sarcolemmal localization of dystrobrevin, syntrophin, and nNOS.
abstract: 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 beta1-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 beta1- and beta2-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 beta1-syntrophin and nNOS.
authors.affiliation: Department of Neuroscience, Brown University, 190 Thayer St., Box 1953, Providence, Rhode Island 02912 USA.
authors.forename: Mary Lynn
authors.initials: ML
authors.lastname: Mercado
authors.forename: Alison R
authors.initials: AR
authors.lastname: Amenta
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hagiwara
authors.forename: Michael S
authors.initials: MS
authors.lastname: Rafii
authors.forename: Beatrice E
authors.initials: BE
authors.lastname: Lechner
authors.forename: Rick T
authors.initials: RT
authors.lastname: Owens
authors.forename: David J
authors.initials: DJ
authors.lastname: McQuillan
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Froehner
authors.forename: Justin R
authors.initials: JR
authors.lastname: Fallon
mesh_terms: D000818:Animals; D058578:Biglycan; D049029:Dystrophin-Associated Proteins / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D032342:Muscle Cells / Q000378:metabolism / Q000648:ultrastructure; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D011509:Proteoglycans / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D012508:Sarcolemma / Q000378:metabolism*; D013347:Subcellular Fractions
chemical_list: C546885:Bgn protein, mouse; D058578:Biglycan; D049029:Dystrophin-Associated Proteins; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; C098885:dystrobrevin; C091824:syntrophin; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse