title: Characterization of the intermolecular associations of the dystrophin-associated glycoprotein complex in retinal Müller glial cells.
abstract: The abnormal retinal neurotransmission observed in Duchenne muscular dystrophy patients has been attributed to altered expression of C-terminal products of the dystrophin gene in this tissue. Müller glial cells from rat retina express dystrophin protein Dp71, utrophin and the members of the dystrophin-associated glycoprotein complex (DGC), namely beta-dystroglycan, delta- and gamma-sarcoglycans and alpha1-syntrophin. The DGC could function in muscle as a link between the cystoskeleton and the extracellular matrix, as well as a signaling complex. However, other than in muscle the composition and intermolecular associations among members of the DGC are still unknown. Here we demonstrate that Dp71 and/or utrophin from rat retinal Müller glial cells form a complex with beta-dystroglycan, delta-sarcoglycan and alpha1-syntrophin. We also show that beta-dystroglycan is associated with alpha-dystrobrevin-1 and PSD-93 and that anti-PSD antibodies coimmunoprecipitated alpha-syntrophin with PSD-93. By overlay experiments we also found that Dp71and/or utrophin and alpha-dystroglycan from Müller cells could bind to actin and laminin, respectively. These results indicate that the DGC could have both structural and signaling functions in retina. On the basis of our accumulated evidence, we propose a hypothetical model for the molecular organization of the dystrophin-associated glycoprotein complex in retinal Müller glial cells, which would be helpful for understanding its function in the central nervous system.
authors.affiliation: Inserm EMI 99-18, Laboratoire de Physiopathologie Moléculaire et Cellulaire de la Rétine, CHRU, France.
authors.forename: T
authors.initials: T
authors.lastname: Claudepierre
authors.forename: C
authors.initials: C
authors.lastname: Dalloz
authors.forename: D
authors.initials: D
authors.lastname: Mornet
authors.forename: K
authors.initials: K
authors.lastname: Matsumura
authors.forename: J
authors.initials: J
authors.lastname: Sahel
authors.forename: A
authors.initials: A
authors.lastname: Rendon
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000276:immunology / Q000378:metabolism*; D049030:Dystroglycans; D016189:Dystrophin / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism*; D049029:Dystrophin-Associated Proteins; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin / Q000378:metabolism; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D008954:Models, Biological; D009124:Muscle Proteins / Q000276:immunology / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism; D009457:Neuroglia / Q000737:chemistry / Q000378:metabolism*; D011233:Precipitin Tests; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000737:chemistry / Q000166:cytology*; D049031:Sarcoglycans; D049411:Utrophin
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C501451:Mpp2 protein, rat; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D049031:Sarcoglycans; D049411:Utrophin; C085339:apo-dystrophin 1; C098885:dystrobrevin; C033652:postsynaptic density proteins; C091825:syntrophin alpha1; D049030:Dystroglycans