Sanny Justina, Chui Vincent, Langmann Caillin, Pereira Carla, Zahedi Baharak, Harden Nicholas
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
Dev Genes Evol. 2006 Sep;216(9):543-50. doi: 10.1007/s00427-006-0067-6. Epub 2006 Apr 12.
The Rho family small GTPases Rho, Rac, and Cdc42 regulate cell shape and motility through the actin cytoskeleton. These proteins cycle between a GTP-bound "on" state and a GDP-bound "off" state and are negatively regulated by GTPase-activating proteins (GAPs), which accelerate the small GTPase's intrinsic hydrolysis of bound GTP to GDP. Drosophila RhoGAP68F is similar to the mammalian protein p50RhoGAP/Cdc42GAP, which exhibits strong GAP activity toward Cdc42. We find that, despite the strong similarities between RhoGAP68F and p50RhoGAP/Cdc42GAP, RhoGAP68F is most effective as a GAP for RhoA. These in vitro data are supported by the in vivo analysis of mutants in RhoGAP68F. We demonstrate through the characterization of two alleles of the RhoGAP68F gene that RhoGAP68F participates in gastrulation of the embryo, a morphogenetic event driven by cell constriction that involves RhoA signaling. We propose that RhoGAP68F functions as a regulator of RhoA signaling during gastrulation.
Rho家族的小GTP酶Rho、Rac和Cdc42通过肌动蛋白细胞骨架调节细胞形状和运动。这些蛋白质在结合GTP的“开启”状态和结合GDP的“关闭”状态之间循环，并受到GTP酶激活蛋白（GAPs）的负调控，GAPs可加速小GTP酶将结合的GTP内在水解为GDP。果蝇RhoGAP68F与哺乳动物蛋白p50RhoGAP/Cdc42GAP相似，后者对Cdc42表现出很强的GAP活性。我们发现，尽管RhoGAP68F与p50RhoGAP/Cdc42GAP有很强的相似性，但RhoGAP68F作为RhoA的GAP最为有效。这些体外数据得到了RhoGAP68F突变体的体内分析的支持。我们通过对RhoGAP68F基因的两个等位基因的表征证明，RhoGAP68F参与胚胎原肠胚形成，这是一种由细胞收缩驱动的形态发生事件，涉及RhoA信号传导。我们提出，RhoGAP68F在原肠胚形成过程中作为RhoA信号的调节因子发挥作用。
