title: Endocytosis-dependent coordination of multiple actin regulators is required for wound healing.
abstract: The ability to heal wounds efficiently is essential for life. After wounding of an epithelium, the cells bordering the wound form dynamic actin protrusions and/or a contractile actomyosin cable, and these actin structures drive wound closure. Despite their importance in wound healing, the molecular mechanisms that regulate the assembly of these actin structures at wound edges are not well understood. In this paper, using Drosophila melanogaster embryos, we demonstrate that Diaphanous, SCAR, and WASp play distinct but overlapping roles in regulating actin assembly during wound healing. Moreover, we show that endocytosis is essential for wound edge actin assembly and wound closure. We identify adherens junctions (AJs) as a key target of endocytosis during wound healing and propose that endocytic remodeling of AJs is required to form "signaling centers" along the wound edge that control actin assembly. We conclude that coordination of actin assembly, AJ remodeling, and membrane traffic is required for the construction of a motile leading edge during wound healing.
authors.affiliation: The Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Matsubayashi
authors.affiliation: The Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK.
authors.forename: Camilla
authors.initials: C
authors.lastname: Coulson-Gilmer
authors.affiliation: The Healing Foundation Centre, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK tom.millard@manchester.ac.uk.
authors.forename: Tom H
authors.initials: TH
authors.lastname: Millard
mesh_terms: D000199:Actins / Q000378:metabolism*; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism; D000080865:Formins; D008840:Microfilament Proteins / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D000199:Actins; D015820:Cadherins; D002352:Carrier Proteins; D002966:Clathrin; D029721:Drosophila Proteins; D000080865:Formins; D008840:Microfilament Proteins; C449671:SCAR protein, Drosophila; C477859:WASp protein, Drosophila; D051316:Wiskott-Aldrich Syndrome Protein; C106890:diaphanous protein, Drosophila; C501889:shg protein, Drosophila