title: Modulation of cell spreading and cell-substrate adhesion dynamics by dystroglycan.
abstract: Dystroglycan is a ubiquitously expressed cell adhesion protein. Its principal role has been determined as a component of the dystrophin-glycoprotein complex of muscle, where it constitutes a key component of the costameric cell adhesion system. To investigate more fundamental aspects of dystroglycan function in cell adhesion, we examined the role of dystroglycan in the dynamics and assembly of cellular adhesions in myoblasts. We show that beta-dystroglycan is recruited to adhesion structures and, based on staining for vinculin, that overexpression or depletion of dystroglycan affects both size and number of fibrillar adhesions. Knockdown of dystroglycan increases the size and number of adhesions, whereas overexpression decreases the number of adhesions. Dystroglycan knockdown or overexpression affects the ability of cells to adhere to different substrates, and has effects on cell migration that are consistent with effects on the formation of fibrillar adhesions. Using an SH3 domain proteomic screen, we identified vinexin as a binding partner for dystroglycan. Furthermore, we show that dystroglycan can interact indirectly with vinculin by binding to the vinculin-binding protein vinexin, and that this interaction has a role in dystroglycan-mediated cell adhesion and spreading. For the first time, we also demonstrate unequivocally that beta-dystroglycan is a resident of focal adhesions.
authors.affiliation: Departments of Biomedical Science, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Thompson
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Moore
authors.forename: Sadaf-Ahmahni
authors.initials: SA
authors.lastname: Hussain
authors.forename: Iivari
authors.initials: I
authors.lastname: Kleino
authors.forename: Michelle
authors.initials: M
authors.lastname: Peckham
authors.forename: Erhard
authors.initials: E
authors.lastname: Hohenester
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: Ayscough
authors.forename: Kalle
authors.initials: K
authors.lastname: Saksela
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Winder
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002461:Cell Line, Transformed; D022081:Cell Surface Extensions / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D049030:Dystroglycans / Q000235:genetics / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D032446:Myoblasts / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D016596:Vinculin / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D016596:Vinculin; D049030:Dystroglycans