XRab40 and XCullin5 form a ubiquitin ligase complex essential for the noncanonical Wnt pathway
XRab40 and XCullin5 form a ubiquitin ligase complex essential for the noncanonical Wnt pathway
复制标题
DOI：
10.1038/sj.emboj.7601781
复制
发表时间：
2007-08-08
期刊：
影响因子：
11.4
通讯作者：
Kinoshita, Noriyuki
中科院分区：
文献类型：
--
作者：
Lee, Rebecca Hui Kwan;Iioka, Hidekazu;Kinoshita, Noriyuki
Rab GTP酶是细胞内膜转运的关键调节因子。我们试图阐明Rab GTP酶在非洲爪哇原肠形成中的作用，并发现正常的原肠形成需要一个非洲爪哇同系物Rab40(XRab40)。XRab40定位于高尔基体，与ElonginB/C和Cullin5相互作用形成泛素连接酶。XRab40/XCullin5协同作用调节Rap2 GTP酶的泛素化和定位。此外，XRab40/XCullin5通过Rap2及其效应因子畸形/NCK相互作用蛋白(XMINK)调节Wnt途径中的关键信号分子Dsh的膜定位。XMINK与Dsh相互作用，并通过Wnt活化转移到质膜上。我们提出了一个由XRab40/XCullin5、Rap2和XMINK组成的新的信号级联，它在非典范Wnt途径的调控中起着至关重要的作用。
Rab GTPases are key regulators of intracellular membrane trafficking. We sought to elucidate the roles of Rab GTPases in Xenopus gastrulation, and found that a Xenopus homolog of Rab40 (XRab40) is required for normal gastrulation. XRab40 is localized at the Golgi apparatus and interacts with ElonginB/C and Cullin5 to form a ubiquitin ligase. XRab40/XCullin5 functions cooperatively and regulates the ubiquitination and localization of Rap2 GTPase. Furthermore, XRab40/XCullin5 regulates the membrane localization of Dishevelled (Dsh), a key signaling molecule in the Wnt pathway, through Rap2 and its effector Misshapen/Nck-interacting kinase (XMINK). XMINK interacts with Dsh, and is translocated to the plasma membrane by Wnt activation. We propose a novel signaling cascade consisting of XRab40/XCullin5, Rap2 and XMINK, which plays a crucial role in the regulation of the noncanonical Wnt pathway.