XRab40 and XCullin5 form a ubiquitin ligase complex essential for the noncanonical Wnt pathway

EMBO J. 2007 Aug 8;26(15):3592-606. doi: 10.1038/sj.emboj.7601781. Epub 2007 Jul 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Protein Binding
  • RNA, Messenger / genetics
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Two-Hybrid System Techniques
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / metabolism*
  • Wnt Proteins / metabolism*
  • Xenopus


  • Membrane Proteins
  • RNA, Messenger
  • Ubiquitin
  • Wnt Proteins
  • Ubiquitin-Protein Ligases