title: A syndecan-4 hair trigger initiates wound healing through caveolin- and RhoG-regulated integrin endocytosis.
abstract: Cell migration during wound healing requires adhesion receptor turnover to enable the formation and disassembly of cell-extracellular matrix contacts. Although recent advances have improved our understanding of integrin trafficking pathways, it is not known how extracellular ligand engagement controls receptor dynamics. Using atomic force microscopy, we have measured cell avidity for fibronectin and defined a mechanism for the outside-in regulation of α(5)β(1)-integrin. Surprisingly, adhesive strength was attenuated by the syndecan-4-binding domain of fibronectin due to a rapid triggering of α(5)β(1)-integrin endocytosis. Association of syndecan-4 with PKCα was found to trigger RhoG activation and subsequent dynamin- and caveolin-dependent integrin uptake. Like disruption of syndecan-4 or caveolin, gene disruption of RhoG in mice was found to retard closure of dermal wounds due to a migration defect of the fibroblasts and keratinocytes of RhoG null mice. Thus, this syndecan-4-regulated integrin endocytic pathway appears to play a key role in tissue repair.
authors: School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UK. mark.bass@bristol.ac.uk
authors: Mark D
authors: MD
authors: Bass
authors: Rosalind C
authors: RC
authors: Williamson
authors: Robert D
authors: RD
authors: Nunan
authors: Jonathan D
authors: JD
authors: Humphries
authors: Adam
authors: A
authors: Byron
authors: Mark R
authors: MR
authors: Morgan
authors: Paul
authors: P
authors: Martin
authors: Martin J
authors: MJ
authors: Humphries
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000502:physiology*; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D004705:Endocytosis; D005109:Extracellular Matrix; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000502:physiology*; D039081:Integrin alpha5beta1 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018625:Microscopy, Atomic Force; D051571:Protein Kinase C-alpha / Q000378:metabolism; D015398:Signal Transduction; D053671:Syndecan-4 / Q000502:physiology*; D014945:Wound Healing; D020741:rho GTP-Binding Proteins
chemical_list: D051242:Caveolin 1; D005353:Fibronectins; D039081:Integrin alpha5beta1; C489577:Rhog protein, mouse; C508306:Sdc4 protein, mouse; D053671:Syndecan-4; D051571:Protein Kinase C-alpha; D020558:GTP Phosphohydrolases; D020741:rho GTP-Binding Proteins