title: A Gαq-Ca²⁺ signaling pathway promotes actin-mediated epidermal wound closure in C. elegans.
abstract: BACKGROUND
  Repair of skin wounds is essential for animals to survive in a harsh environment, yet the signaling pathways initiating wound repair in vivo remain little understood. In Caenorhabditis elegans, a p38 mitogen-activated protein kinase (MAPK) cascade promotes innate immune responses to wounding but is not required for other aspects of wound healing. We therefore set out to identify additional wound response pathways in C. elegans epidermis.
  
  
  RESULTS
  We show here that wounding the adult C. elegans skin triggers a rapid and sustained rise in epidermal Ca(2+) that is critical for survival after wounding. The wound-triggered rise in Ca(2+) requires the epidermal transient receptor potential channel, melastatin family (TRPM) channel GTL-2 and IP(3)R-stimulated release from internal stores. We identify an epidermal signal transduction pathway that includes the Gα(q) EGL-30 and its effector PLCβ EGL-8. Loss of function in this pathway impairs survival after wounding. The Gα(q)-Ca(2+) pathway is not required for known innate immune responses to wounding but instead promotes actin-dependent wound closure. Wound closure requires the Cdc42 small GTPase and Arp2/3-dependent actin polymerization and is negatively regulated by Rho and nonmuscle myosin. Finally, we show that the death-associated protein kinase DAPK-1 acts as a negative regulator of wound closure.
  
  
  CONCLUSIONS
  Skin wounding in C. elegans triggers a Ca(2+)-dependent signaling cascade that promotes wound closure, in parallel to the innate immune response to damage. Wound closure requires actin polymerization and is negatively regulated by nonmuscle myosin.
authors.affiliation: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Suhong
authors.initials: S
authors.lastname: Xu
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Chisholm
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000276:immunology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D064550:Death-Associated Protein Kinases; D004817:Epidermis / Q000276:immunology* / Q000293:injuries; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D054799:Phospholipase C beta / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000276:immunology*; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D050053:TRPM Cation Channels / Q000378:metabolism; D014945:Wound Healing / Q000276:immunology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; C479565:Egl-30 protein, C elegans; C554835:GTL-2 protein, C elegans; D050053:TRPM Cation Channels; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517632:Egl-8 protein, C elegans; D054799:Phospholipase C beta; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D002118:Calcium
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