Regulation of collective cell migration by RhoGAP myosin IXA.
Collective cell migration is a key process during epithelial morphogenesis, tissue regeneration and tumor dissemination. During collective epithelial migration, anterior-posterior polarity, apical-basal polarity and cell-cell junctions must be dynamically coordinated, but the underlying molecular mechanisms controlling this complex behavior are unclear. Rho GTPases regulate the actin cytoskeleton, in particular protrusive and contractile activities at cell-cell contacts. Recently, a number of regulators - nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) - have been identified and suggested to provide spatio-temporal control of Rho GTPases at cell-cell contacts. One of these is myosin IXA, a member of class IX, single-headed actin motors having a conserved RhoGAP domain. Using its actin-binding and motor activities, myosin IX interacts with actin filaments and moves toward filament plus ends. At the plasma membrane, myosin IX's RhoGAP activity negatively regulates Rho to facilitate localized reorganization of the actin cytoskeleton. Here, I discuss how myosin IXA regulates Rho and the actin cytoskeleton during the assembly of nascent cell-cell contacts and how this might contribute to collective epithelial migration.
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. omelchet@mskcc.org
Tatiana
T
Omelchenko
D000199:Actins / Q000502:physiology; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000502:physiology*; D006801:Humans; D009218:Myosins / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000502:physiology*
D000199:Actins; D020690:GTPase-Activating Proteins; C120896:MYO9A protein, human; C085379:rho GTPase-activating protein; D009218:Myosins; D020741:rho GTP-Binding Proteins