| Research Abstract |
The Rho family GTPases (Rho, Rac, and Cdc42) regulate cytoskeletons and cell adhesions through their specific effectors. However, the molecular mechanisms by which the Rho family GTPases regulate these cellular functions have been unknown. Recently, we found that Rho-kinase, an effector of Rho, regulates actin cytoskeleton by regulating the phosphorylation state of myosin light chain (MLC) and that IQGAP1, an effector of Rac and Cdc42, regulates cadherin-mediated cell-cell adhesion. The aim of the present study is to further clarify the mechanism how Rho family GTPases and their effectors regulate cytoskeletons and cell adhesions. Here we found several novel substrates of Rho-kinase : CRMP-2, adducin, MAP2, tau, calponin and EF-1α. CRMP-2 phosphorylation by Rho-kinase was involved in LPA-induced growth cone collapse. We also found that adducin phosphorylation by Rho-kinase modulated cell migration. The analysis of the physiological functions of their phosphorylations is on going. In addition, we demonstrated that the Cdc42/Rac/IQGAP1 system was involved in cell-cell dissociation during cell scattering through α-catenin relocalization. The results obtained here lead us to better understanding how Rho family GTPases regulate cytoskeletons and cell
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