A Syndecan-4 Hair Trigger Initiates Wound Healing through Caveolin- and RhoG-Regulated Integrin Endocytosis
| Autor: | Paul Martin, Mark D. Bass, Robert Nunan, Martin J. Humphries, Adam Byron, Jonathan D. Humphries, Rosalind C. Williamson, Mark R. Morgan |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Keratinocytes
rho GTP-Binding Proteins Protein Kinase C-alpha Endocytic cycle Integrin Caveolin 1 030204 cardiovascular system & hematology Microscopy Atomic Force General Biochemistry Genetics and Molecular Biology Article GTP Phosphohydrolases 03 medical and health sciences Mice 0302 clinical medicine Cell Movement Caveolin Cell Adhesion Animals Molecular Biology Cells Cultured Dynamin 030304 developmental biology 0303 health sciences Wound Healing biology Cell migration Cell Biology Fibroblasts Endocytosis Cell biology Extracellular Matrix Fibronectins Fibronectin 030220 oncology & carcinogenesis biology.protein Syndecan-4 RhoG Erratum Integrin alpha5beta1 Signal Transduction Developmental Biology |
| Zdroj: | Developmental Cell |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2011.08.007 |
| Popis: | Summary 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 α5β1-integrin. Surprisingly, adhesive strength was attenuated by the syndecan-4-binding domain of fibronectin due to a rapid triggering of α5β1-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. Graphical Abstract Highlights ► Syndecan-4 engagement mobilizes cells by reducing avidity for extracellular matrix ► Syndecan-4 induces caveolin-mediated endocytosis rather than inactivation of integrin ► Matrix ligands of syndecan-4 cause RhoG activation, which triggers endocytosis ► Gene disruption of syndecan-4, RhoG, or caveolin-1 results in compromised wound healing |
| Databáze: | OpenAIRE |
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