Espinosa Eric J, Calero Monica, Sridevi Khambhampaty, Pfeffer Suzanne R
Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5307, USA.
Cell. 2009 May 29;137(5):938-48. doi: 10.1016/j.cell.2009.03.043.
Rho GTPases are key regulators of the actin-based cytoskeleton; Rab GTPases are key regulators of membrane traffic. We report here that the atypical Rho GTPase family member, RhoBTB3, binds directly to Rab9 GTPase and functions with Rab9 in protein transport from endosomes to the trans Golgi network. Gene replacement experiments show that RhoBTB3 function in cultured cells requires both RhoBTB3's N-terminal, Rho-related domain and C-terminal sequences that are important for Rab9 interaction. Biochemical analysis reveals that RhoBTB3 binds and hydrolyzes ATP rather than GTP. Rab9 binding opens the autoinhibited RhoBTB3 protein to permit maximal ATP hydrolysis. Because RhoBTB3 interacts with TIP47 on membranes, we propose that it may function to release this cargo selection protein from vesicles to permit their efficient docking and fusion at the Golgi.
Rho GTP酶是基于肌动蛋白的细胞骨架的关键调节因子；Rab GTP酶是膜运输的关键调节因子。我们在此报告，非典型Rho GTP酶家族成员RhoBTB3直接与Rab9 GTP酶结合，并在蛋白质从内体运输到反式高尔基体网络的过程中与Rab9协同发挥作用。基因替代实验表明，RhoBTB3在培养细胞中的功能既需要RhoBTB3的N端、与Rho相关的结构域，也需要对Rab9相互作用很重要的C端序列。生化分析表明，RhoBTB3结合并水解ATP而非GTP。Rab9的结合打开了自抑制的RhoBTB3蛋白，以允许最大程度的ATP水解。由于RhoBTB3与膜上的TIP47相互作用，我们提出它可能起到从囊泡中释放这种货物选择蛋白的作用，以使其在高尔基体处高效对接和融合。
