The spreading of adhering cells is a morphogenetic process during which cells break spherical or radial symmetry and adopt migratory polarity with spatially segregated protruding cell front and non-protruding cell rear. The organization and regulation of these symmetry-breaking events, which are both complex and stochastic, are not fully understood. Here we show that in radially spreading cells, symmetry breaking commences with the development of discrete non-protruding regions characterized by large but sparse focal adhesions and long peripheral actin bundles. Establishment of this non-protruding static region specifies the distally oriented protruding cell front and thus determines the polarity axis and the direction of cell migration. The development of non-protruding regions requires ERK2 and the ERK pathway scaffold protein RACK1. RACK1 promotes adhesion-mediated activation of ERK2 that in turn inhibits p190A-RhoGAP signaling by reducing the peripheral localization of p190A-RhoGAP. We propose that sustained ERK signaling at the prospective cell rear induces p190A-RhoGAP depletion from the cell periphery resulting in peripheral actin bundles and cell rear formation. Since cell adhesion activates both ERK and p190A-RhoGAP signaling this constitutes a spatially confined incoherent feed-forward signaling circuit.

• MeSH
• aktiny metabolismus   MeSH
• biologické modely MeSH
• buněčná adheze MeSH
• fenotyp MeSH
• fibroblasty cytologie   enzymologie   metabolismus   MeSH
• fokální adhezní tyrosinkinasy metabolismus   MeSH
• genový knockdown MeSH
• krysa rodu rattus MeSH
• MAP kinasový signální systém * MeSH
• mitogenem aktivovaná proteinkinasa 1 metabolismus   MeSH
• pohyb buněk MeSH
• proteiny vázající GTP nedostatek   metabolismus   MeSH
• represorové proteiny metabolismus   MeSH
• tvar buňky MeSH
• umlčování genů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH