Article
- The EMBO Journal (2007) 26, 3592 - 3606
- doi:10.1038/sj.emboj.7601781
Published online: 12 July 2007
Subject Categories:
XRab40 and XCullin5 form a ubiquitin ligase complex essential for the noncanonical Wnt pathway
Rebecca Hui Kwan Lee1,2, Hidekazu Iioka1, Masato Ohashi3, Shun-ichiro Iemura4, Tohru Natsume4 and Noriyuki Kinoshita1,2
- Department of Developmental Biology, National Institute for Basic Biology, Okazaki, Aichi, Japan
- Department of Molecular Biomechanics, The Graduate University for Advanced Studies; Okazaki, Aichi, Japan
- Okazaki Institute for Integrative Bioscience, National Institute of Natural Sciences, Okazaki, Japan
- National Institutes of Advanced Industrial Science and Technology; Biological Information Research Center; Tokyo, Japan
Correspondence to:
Noriyuki Kinoshita, Department of Developmental Biology, National Institute for Basic Biology, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan. Tel.: +81 564 55 7573; Fax: +81 564 55 7571; E-mail: nkinoshi@nibb.ac.jp
Received 6 March 2007; Accepted 11 June 2007
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.
Keywords:
- gastrulation,
- Rab GTPase,
- ubiquitination,
- Wnt signaling,
- Xenopus
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
NEWS AND VIEWS
A role for Wnts in morpho-genesis and tissue polarity
Nature Cell Biology News and Views (01 Jul 2000)
Ephrins make eyes with planar cell polarity
Nature Cell Biology News and Views (01 Jan 2006)
RESEARCH
Identification of IGFBP-6 as an effector of the tumor suppressor activity of SEMA3B
Oncogene Original Article
Nature Cell Biology Article (01 Apr 2006)
