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 Elongin...

Full description

Saved in:
Bibliographic Details
Published in:The EMBO journal 2007-08, Vol.26 (15), p.3592-3606
Main Authors: Lee, Rebecca Hui Kwan, Iioka, Hidekazu, Ohashi, Masato, Iemura, Shun-ichiro, Natsume, Tohru, Kinoshita, Noriyuki
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Cellular biology
EMBO11
EMBO37
gastrulation
Membrane Proteins - chemistry
Membrane Proteins - genetics
Membrane Proteins - metabolism
Membranes
Molecular biology
Molecular Sequence Data
Protein Binding
Rab GTPase
RNA, Messenger - genetics
Sequence Homology, Amino Acid
Signal transduction
Substrate Specificity
Two-Hybrid System Techniques
Ubiquitin - metabolism
Ubiquitin-Protein Ligases - metabolism
ubiquitination
Wnt Proteins - metabolism
Wnt signaling
Xenopus
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7601781