A role for syndecan-1 in coupling fascin spike formation by thrombospondin-1.
An important role of cell matrix adhesion receptors is to mediate transmembrane coupling between extracellular matrix attachment, actin reorganization, and cell spreading. Thrombospondin (TSP)-1 is a modulatory component of matrix expressed during development, immune response, or wound repair. Cell adhesion to TSP-1 involves formation of biochemically distinct matrix contacts based on stable fascin spikes. The cell surface adhesion receptors required have not been identified. We report here that antibody clustering of syndecan-1 proteoglycan specifically transduces organization of cortical actin and fascin bundles in several cell types. Transfection of COS-7 cells with syndecan-1 is sufficient to stimulate cell spreading, fascin spike assembly, and extensive protrusive lateral ruffling on TSP-1 or on syndecan-1 antibody. The underlying molecular mechanism depends on glycosaminoglycan (GAG) modification of the syndecan-1 core protein at residues S45 or S47 for cell membrane spreading and on the VC2 region of the cytoplasmic domain for spreading and fascin spike formation. Expression of the VC2 deletion mutant or GAG-negative syndecan-1 showed that syndecan-1 is necessary in spreading and fascin spike formation by C2C12 cells on TSP-1. These results establish a novel role for syndecan-1 protein in coupling a physiological matrix ligand to formation of a specific matrix contact structure.
Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom. dmcbjca@ucl.ac.uk
J C
JC
Adams
N
N
Kureishy
A L
AL
Taylor
D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D018955:CD36 Antigens / Q000378:metabolism; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002465:Cell Movement / Q000502:physiology*; D002469:Cell Separation; D022081:Cell Surface Extensions / Q000378:metabolism*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D003599:Cytoskeleton / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D005434:Flow Cytometry; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D016023:Integrins / Q000276:immunology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D011509:Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D053668:Syndecan-1; D053667:Syndecans; D019700:Thrombospondin 1 / Q000378:metabolism*; D014162:Transfection; D016596:Vinculin / Q000378:metabolism
D000199:Actins; D015703:Antigens, CD; D018955:CD36 Antigens; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; C497895:Cd47 protein, mouse; D002614:Chelating Agents; D016895:Culture Media, Serum-Free; D006025:Glycosaminoglycans; D016023:Integrins; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; D019700:Thrombospondin 1; D016596:Vinculin; C020324:fascin; D004492:Edetic Acid