title: XRab40 and XCullin5 form a ubiquitin ligase complex essential for the noncanonical Wnt pathway.
abstract: 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.
authors.affiliation: Department of Developmental Biology, National Institute for Basic Biology, Okazaki, Aichi, Japan.
authors.forename: Rebecca Hui Kwan
authors.initials: RH
authors.lastname: Lee
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Iioka
authors.forename: Masato
authors.initials: M
authors.lastname: Ohashi
authors.forename: Shun-Ichiro
authors.initials: S
authors.lastname: Iemura
authors.forename: Tohru
authors.initials: T
authors.lastname: Natsume
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kinoshita
mesh_terms: 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
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; D025801:Ubiquitin; D051153:Wnt Proteins; D044767:Ubiquitin-Protein Ligases