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Disruption of perlecan binding and matrix assembly by post-translational or genetic disruption of dystroglycan function

Department of Physiology and Biophysics, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, 400 Eckstein Medical Building, Iowa City, IA 52242, USA.
FEBS Letters (Impact Factor: 3.34). 09/2005; 579(21):4792-6. DOI: 10.1016/j.febslet.2005.07.059
Source: PubMed

ABSTRACT Dystroglycan is a cell-surface matrix receptor that requires LARGE-dependent glycosylation for laminin binding. Although the interaction of dystroglycan with laminin has been well characterized, less is known about the role of dystroglycan glycosylation in the binding and assembly of perlecan. We report reduced perlecan-binding activity and mislocalization of perlecan in the LARGE-deficient Large(myd) mouse. Cell-surface ligand clustering assays show that laminin polymerization promotes perlecan assembly. Solid-phase binding assays provide evidence for the first time of a trimolecular complex formation of dystroglycan, laminin and perlecan. These data suggest functional disruption of the trimolecular complex in glycosylation-deficient muscular dystrophy.

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Available from: Kevin P Campbell, Jul 28, 2015
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    • "The α-DG is modified by three different types of glycans such as: mucin type O-glycosylation, O-mannosylation, and N-glycosylation. The glycosylated α-DG is essential for the protein's ability to bind the laminin globular domaincontaining proteins of the Extracellular Matrix (Kanagawa, 2005). LARGE is required for the generation of functional, properly glycosylated forms of α-DG (Barresi, 2004). "
    Computational Biology and Applied Bioinformatics, 09/2011; , ISBN: 978-953-307-629-4
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    • "Dystroglycan is encoded by a single gene (DAG1) and is cleaved into two proteins, a-dystroglycan (a-DG) and b-dystroglycan (b-DG), by posttranslational processing (Ibraghimov-Beskrovnaya et al., 1992). DGs are central components of the dystrophin– glycoprotein complex (DGC) at the sarcolemma, and a-DG was shown to serve as a cell surface receptor for laminin (Ibraghimov-Beskrovnaya et al., 1992), agrin (Gee et al., 1994; Campanelli et al., 1994), perlecan (Peng et al., 1998; Kanagawa et al., 2005), and neurexin (Sugita et al., 2001). In skeletal muscle , the laminin-a-DG linkage is thought to be critical for plasma membrane stability (recently reviewed in Kanagawa and Toda 2006). "
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    • "On the external surface of the sarcolemma, components of the dystrophin–glycoprotein complex have been shown to interact with several constituents of the extracellular matrix. Through its incompletely characterized carbohydrate epitopes (Section 2.1), a-dystroglycan has been shown to interact with laminins (Ibraghimov-Beskrovnaya et al., 1992; Ervasti and Campbell, 1993), agrins (Bowe et al., 1994; Campanelli et al., 1994; Gee et al., 1994; Sugiyama et al., 1994), and perlecan (Talts et al., 1999; Peng et al., 1999; Kanagawa et al., 2005), which all bind a-dystroglycan through a conserved G-domain motif (Gee et al., 1993; Hohenester et al., 1999). Laminin-2 is the predominant laminin isoform expressed in striated muscle (Patton et al., 1997) and mutations leading to laminin-2 deficiency cause forms of congenital muscular dystrophy (Xu et al., 1994; Sunada et al., 1994; Helbling-Leclerc et al., 1995). "
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