Novel regulation and dynamics of myosin II activation during epidermal wound responses.
Wound healing in the skin is an important and complex process that involves 3-dimensional tissue reorganization, including matrix and chemokine-triggered cell migration, paracrine signaling, and matrix remodeling. The molecular signals and underlying mechanisms that stimulate myosin II activity during skin wound healing have not been elucidated. To begin understanding the signaling pathways involved in the activation of myosin II in this process, we have evaluated myosin II activation in migrating primary human keratinocytes in response to scratch wounding in vitro. We report here that myosin II activation and recruitment to the cytoskeleton in wounded keratinocytes are biphasic. Post-wounding, a rapid phosphorylation of myosin II regulatory light chain (RLC) occurs with resultant translocation of myosin IIA to the cell cortex, far in advance of the later polarization and cell migration. During this acute-phase of myosin II activation, pharmacological approaches reveal p38-MAP kinase and cytosolic calcium as having critical roles in the phosphorylation driving cytoskeletal assembly. Although p38-MAPK has known roles in keratinocyte migration, and known roles in leading-edge focal complex dynamics, to our knowledge this is the first report of p38-MAPK acting as an upstream activator of myosin II phosphorylation and assembly during any type of wound response.
Betapudi
Venkaiah
V
Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Rai
Vandana
V
Beach
Jordan R
JR
Egelhoff
Thomas
T
D002465:Cell Movement / Q000502:physiology; D004791:Enzyme Inhibitors / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000473:pathology* / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D024501:Nonmuscle Myosin Type IIB / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D004791:Enzyme Inhibitors; C466107:MRLC2 protein, human; D018994:Myosin Light Chains; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D024507:Nonmuscle Myosin Type IIA; D024501:Nonmuscle Myosin Type IIB; D018995:Myosin Heavy Chains