Regulation of epidermal growth factor receptor traffic by the small GTPase RhoB
Regulation of epidermal growth factor receptor traffic by the small GTPase RhoB
复制标题
DOI：
10.1016/s0960-9822(99)80422-9
复制
发表时间：
1999-09-09
期刊：
影响因子：
9.2
通讯作者：
Mellor, H
中科院分区：
文献类型：
--
作者：
Gampel, A;Parker, PJ;Mellor, H
Rho家族的小分子GTP酶通过对肌动蛋白细胞骨架的动态调节来控制细胞的黏附和运动。虽然已经确定了12个家庭成员，但只有3个成员RhoA、Pac和Cdc42-得到了详细的研究。RhoA调节局部粘连的形成和将肌动蛋白细丝捆绑成应力纤维。它还参与其他细胞信号通路，包括基因表达的调节和脂质第二信使的产生[1，2]。RhoA与另外两个鲜为人知的小GTP酶关系密切：RhoB和RhoC(这两个酶大约83%相同)。其中最耐人寻味的或许是RhoB。RhoA在很大程度上是胞浆的，但在激活时转移到质膜。然而，RhoB完全定位于内吞小泡的胞液表面[3，4]，这表明RhoB在调节内吞运输方面具有潜在的作用；然而，没有证据支持这一点。RhoA已被证明在质膜上起作用，调节笼蛋白介导的转铁蛋白受体[5]和M碱乙酰胆碱受体[6]的内化。我们最近证明了RhoB结合了RhoA效应器PRK1，并将其靶向到内膜室[7]。我们在这里表明，RhoB通过PRK1调节表皮生长因子受体运输的动力学。
Members of the Rho family of small GTPases control cell adhesion and motility through dynamic regulation of the actin cytoskeleton. Although twelve family members have been identified, only three of these RhoA, Pac and Cdc42 - have been studied in detail. RhoA regulates the formation of focal adhesions and the bundling of actin filaments into stress fibres. It is also involved in other cell signalling pathways including the regulation of gene expression and the generation of lipid second messengers [1,2]. RhoA is very closely related to two other small GTPases about which much less is known: RhoB and RhoC (which are approximately 83% identical). Perhaps the most intriguing of these is RhoB. RhoA is largely cytosolic but translocates to the plasma membrane on activation. RhoB, however, is entirely localised to the cytosolic face of endocytic vesicles [3,4], This suggests a potential role for RhoB in regulating endocytic traffic; however, no evidence has been presented to support this. RhoA has been shown to act at the plasma membrane to regulate the clathrin mediated internalisation of transferrin receptor [5] and of the muscarinic acetylcholine receptor [6]. We have recently demonstrated that RhoB binds the RhoA effector, PRK1 and targets it to the endosomal compartment [7]. We show here that RhoB acts through PRK1 to regulate the kinetics of epidermal growth factor receptor traffic.