title: Integrin-syndecan cooperation governs the assembly of signalling complexes during cell spreading.
abstract: Cell adhesion to fibronectin (FN) triggers the formation and maturation of adhesion complexes by modulating the activity of the Rho family of GTPases. Cells plated onto a ligand of integrin alpha5beta1 spread but fail to form focal adhesions or fully organize actin into bundled stress fibres unless co-stimulated with a ligand of syndecan 4. Engagement of syndecan 4 in such pre-spread cells recapitulates the Rac1 and RhoA activation profiles observed during spreading on whole FN. Furthermore, since adhesion to a ligand of alpha5beta1 alone does not activate Rac1, engagement of syndecan 4 appears to be an absolute requirement. In related work, we have examined differences in the mechanism of focal adhesion formation mediated by the FN-binding integrins alpha4beta1 and alpha5beta1. Two signalling differences were found. First, while alpha5beta1 required syndecan 4 as a co-receptor, alpha4beta1 did not. Second, focal adhesion formation via alpha5beta1 required PKCalpha activation, but only basal PKCalpha activity was observed following adhesion via alpha4beta1. These findings demonstrate that different integrins can signal to induce focal adhesion formation by different mechanisms.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, UK.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Humphries
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Mostafavi-Pour
authors.forename: Mark R
authors.initials: MR
authors.lastname: Morgan
authors.forename: Nicholas O
authors.initials: NO
authors.lastname: Deakin
authors.forename: Anthea J
authors.initials: AJ
authors.lastname: Messent
authors.forename: Mark D
authors.initials: MD
authors.lastname: Bass
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D048430:Cell Shape; D005347:Fibroblasts / Q000166:cytology; D005353:Fibronectins / Q000737:chemistry; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D015398:Signal Transduction; D053667:Syndecans; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D005353:Fibronectins; D039081:Integrin alpha5beta1; D016023:Integrins; D008562:Membrane Glycoproteins; D046912:Multiprotein Complexes; D011509:Proteoglycans; D053667:Syndecans; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein