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A syndecan-4 hair trigger initiates wound healing through caveolin- and RhoG-regulated integrin endocytosis

Bass, Mark D., Williamson, Rosalind C., Nunan, Robert D., Humphries, Jonathan D., Byron, Adam, Morgan, Mark R., Martin, Paul and Humphries, Martin J. 2011. A syndecan-4 hair trigger initiates wound healing through caveolin- and RhoG-regulated integrin endocytosis. Developmental Cell 21 (4) , pp. 681-693. 10.1016/j.devcel.2011.08.007

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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 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QP Physiology
Q Science > QR Microbiology > QR180 Immunology
Publisher: Elsevier
ISSN: 1534-5807
Last Modified: 04 Jun 2017 05:06
URI: http://orca-mwe.cf.ac.uk/id/eprint/48480

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