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Integration of Single and Multicellular Wound Responses

2009; Elsevier BV; Volume: 19; Issue: 16 Linguagem: Inglês

10.1016/j.cub.2009.06.044

1879-0445

Andrew G. Clark, Ann L. Miller, Emily M. Vaughan, Hoi-Ying E. Yu, Rhiannon R. Penkert, William M. Bement,

Marine Biology and Environmental Chemistry

Single cells and multicellular tissues rapidly heal wounds. These processes are considered distinct, but one mode of healing—Rho GTPase-dependent formation and closure of a purse string of actin filaments (F-actin) and myosin-2 around wounds—occurs in single cells [1Bement W.M. Mandato C.A. Kirsch M.N. Wound-induced assembly and closure of an actomyosin purse string in Xenopus oocytes.Curr. Biol. 1999; 9: 579-587Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar, 2Benink H.A. Bement W.M. Concentric zones of active RhoA and Cdc42 around single cell wounds.J. Cell Biol. 2005; 168: 429-439Crossref PubMed Scopus (214) Google Scholar] and in epithelia [3Martin P. Lewis J. Actin cables and epidermal movement in embryonic wound healing.Nature. 1992; 360: 179-183Crossref PubMed Scopus (311) Google Scholar, 4Bement W.M. Forscher P. Mooseker M.S. A novel cytoskeletal structure involved in purse string wound closure and cell polarity maintenance.J. Cell Biol. 1993; 121: 565-578Crossref PubMed Scopus (248) Google Scholar, 5Brock J. Midwinter K. Lewis J. Martin P. Healing of incisional wounds in the embryonic chick wing bud: characterization of the actin purse-string and demonstration of a requirement for Rho activation.J. Cell Biol. 1996; 135: 1097-1107Crossref PubMed Scopus (181) Google Scholar, 6Davidson L.A. Ezin A.M. Keller R. Embryonic wound healing by apical contraction and ingression in Xenopus laevis.Cell Motil. Cytoskeleton. 2002; 53: 163-176Crossref PubMed Scopus (57) Google Scholar, 7Florian P. Schöneberg T. Schulzke J.D. Fromm M. Gitter A.H. Single-cell epithelial defects close rapidly by an actinomyosin purse string mechanism with functional tight junctions.J. Physiol. 2002; 545: 485-499Crossref PubMed Scopus (61) Google Scholar, 8Kofron M. Heasman J. Lang S.A. Wylie C.C. Plakoglobin is required for maintenance of the cortical actin skeleton in early Xenopus embryos and for cdc42-mediated wound healing.J. Cell Biol. 2002; 158: 695-708Crossref PubMed Scopus (33) Google Scholar, 9Wood W. Jacinto A. Grose R. Woolner S. Gale J. Wilson C. Martin P. Wound healing recapitulates morphogenesis in Drosophila embryos.Nat. Cell Biol. 2002; 4: 907-912Crossref PubMed Scopus (294) Google Scholar, 10Russo J.M. Florian P. Shen L. Graham W.V. Tretiakova M.S. Gitter A.H. Mrsny R.J. Turner J.R. Distinct temporal-spatial roles for rho kinase and myosin light chain kinase in epithelial purse-string wound closure.Gastroenterology. 2005; 128: 987-1001Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar]. Here, we show that wounding of one cell in Xenopus embryos elicits Rho GTPase activation around the wound and at the nearest cell-cell junctions in the neighbor cells. F-actin and myosin-2 accumulate at the junctions and around the wound itself, and as the resultant actomyosin array closes over the wound site, junctional F-actin and myosin-2 become mechanically integrated with the actin and myosin-2 around the wound, forming a hybrid purse string. When cells are ablated rather than wounded, Rho GTPase activation and F-actin accumulation occur at cell-cell junctions surrounding the ablated cell, and the purse string closes the hole in the epithelium. Elevation of intracellular free calcium, an essential upstream signal for the single-cell wound response [2Benink H.A. Bement W.M. Concentric zones of active RhoA and Cdc42 around single cell wounds.J. Cell Biol. 2005; 168: 429-439Crossref PubMed Scopus (214) Google Scholar, 11McNeil P.L. Steinhardt R.A. Plasma membrane disruption: repair, prevention, adaptation.Annu. Rev. Cell Dev. Biol. 2003; 19: 697-731Crossref PubMed Scopus (347) Google Scholar], also occurs at the cell-cell contacts and in neighbor cells. Thus, the single and multicellular purse string wound responses represent points on a signaling and mechanical continuum that are integrated by cell-cell junctions.