XRab40 and XCullin5 form a ubiquitin ligase complex essential for the noncanonical Wnt pathway.
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.
Lee
Rebecca Hui Kwan
RH
Department of Developmental Biology, National Institute for Basic Biology, Okazaki, Aichi, Japan.
Iioka
Hidekazu
H
Ohashi
Masato
M
Iemura
Shun-Ichiro
S
Natsume
Tohru
T
Kinoshita
Noriyuki
N
D000595:Amino Acid Sequence; D000818:Animals; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D014981:Xenopus
D008565:Membrane Proteins; D012333:RNA, Messenger; D025801:Ubiquitin; D051153:Wnt Proteins; D044767:Ubiquitin-Protein Ligases