Signal Transduction and Biological Significance of the Small GTPase Rho

点击翻译按钮获取中文摘要

1.The property and function of mDial were studied. It was shown: (1) mDial produces long straight actin filament in the cell by exerting its actin nucleation and polymerization activity, (2) mDial links Rho to Rac ac)tivation through c-Src-Cas-DOCK180 pathway, and antagonizes contractile action of the Rho-ROCK pathway, (3) the balance of the mDial and ROCK determines the cell morphology, a typical example being neurite extension in which the Rho-mDial pathwa extends and the Rho-ROCK pathway retracts neurites dependent on the level of GTP-Rho, and (4) mDial regulates polarity and adhesion turnover in migrating cells and functions in directed cell migration.2.The regulation and function of Rho GTPases in cell division were studied. It was shown: (1) Cdc42 is specifically activated in metaphase and this activation is regulated by a Rho-GEF, ECT2, and a Rho-GAP, MgcRacGAP, (2) Cdc42 acts on a mDia isoform, mDia3, present at the kinetochore, and this pathway contribute biorient binding of the spndle microtubules to the knetochore, thereby regulating chromosome congression in metaphase.3.Mice deficient in either one of the two ROCK isoforms, ROCK-I or ROCK-II, individually, were generated and their phenotypes were studied. This study has elucidated the importance of ROCK-II in homeostatic regulation of placental circulation and that of both isoforms in tissue closure during development. The absence of ROCK-II induces throm4.5.bosis in the placenta and causes intrauterine growth retardation, and the loss of either isoform results in open eye at birth and omphalocele due to impaied closure of the eyelids and ventral body wall.