title: Polarized E-cadherin endocytosis directs actomyosin remodeling during embryonic wound repair.
abstract: Embryonic epithelia have a remarkable ability to rapidly repair wounds. A supracellular actomyosin cable around the wound coordinates cellular movements and promotes wound closure. Actomyosin cable formation is accompanied by junctional rearrangements at the wound margin. We used in vivo time-lapse quantitative microscopy to show that clathrin, dynamin, and the ADP-ribosylation factor 6, three components of the endocytic machinery, accumulate around wounds in Drosophila melanogaster embryos in a process that requires calcium signaling and actomyosin contractility. Blocking endocytosis with pharmacological or genetic approaches disrupted wound repair. The defect in wound closure was accompanied by impaired removal of E-cadherin from the wound edge and defective actomyosin cable assembly. E-cadherin overexpression also resulted in reduced actin accumulation around wounds and slower wound closure. Reducing E-cadherin levels in embryos in which endocytosis was blocked rescued actin localization to the wound margin. Our results demonstrate a central role for endocytosis in wound healing and indicate that polarized E-cadherin endocytosis is necessary for actomyosin remodeling during embryonic wound repair.
authors: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario M5S 3G5, Canada.
authors: Miranda V
authors: MV
authors: Hunter
authors: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario M5S 3G5, Canada.
authors: Donghoon M
authors: DM
authors: Lee
authors: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario M5S 3G5, Canada.
authors: Tony J C
authors: TJ
authors: Harris
authors: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario M5S 3G5, Canada Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada rodrigo.fernandez.gonzalez@utoronto.ca.
authors: Rodrigo
authors: R
authors: Fernandez-Gonzalez
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D008841:Actin Cytoskeleton / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002966:Clathrin / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D018715:Microscopy, Video; D059008:Time-Lapse Imaging; D014945:Wound Healing / Q000502:physiology*
chemical_list: D000089982:ADP-Ribosylation Factor 6; D015820:Cadherins; D002966:Clathrin; D049452:Green Fluorescent Proteins; D000205:Actomyosin; D020727:ADP-Ribosylation Factors; D034281:Dynamins