"New Principles for Regulation of Cytoskeletal Dynamics by Rho GTPases"

A broad variety of fundamental biological processes ranging from morphogenesis, to wound repair to cell division are controlled by the small GTPases of the Rho family--Rho, Rac and Cdc42. In this presentation, aspects of Rho GTPase regulation and function are assessed in two models: repair of cellular wounds and cytokinesis. We find that during cellular repair, Rho and Cdc42 are activated in complementary regions "zones" around wounds, and that this activation results from processes that bear similarity to pattern formation systems in developing animals. We also find that the Rho GTPase zones, which close inward in concert with circumferential actomyosin arrays, do so in an unexpected way--by virtue of spatially biased flux through the GTPase cycle or, to put it another way, a circular wave of activation and inactivation. We also find that waves of Rho activity accompany cytokinesis, that these waves are controlled by the basic cell cycle machinery and, remarkably, are antagonized by actin filaments. It is proposed that spatially biased flux through the GTPase cycle is a basic feature of Rho GTPase behavior and that the resultant waves are important for wound repair and cytokinesis.