The E3 Ubiquitin Ligase AIP4 Mediates Ubiquitination and Sorting of the G Protein-Coupled Receptor CXCR4
Open Access
- 1 November 2003
- journal article
- research article
- Published by Elsevier BV in Developmental Cell
- Vol. 5 (5), 709-722
- https://doi.org/10.1016/s1534-5807(03)00321-6
Abstract
Ubiquitination of the chemokine receptor CXCR4 serves as a targeting signal for lysosomal degradation, but the mechanisms mediating ubiquitination and lysosomal sorting remain poorly understood. Here we report that the Nedd4-like E3 ubiquitin ligase AIP4 mediates ubiquitination of CXCR4 at the plasma membrane, and of the ubiquitin binding protein Hrs on endosomes. CXCR4 activation promotes CXCR4 colocalization with AIP4 and Hrs within the same region of endosomes. Endosomal sorting of CXCR4 is dependent on Hrs as well as the AAA ATPase Vps4, the latter involved in regulating the ubiquitination status of both CXCR4 and Hrs. We propose a model whereby AIP4, Hrs, and Vps4 coordinate a cascade of ubiquitination and deubiquitination events that sort CXCR4 to the degradative pathway.Keywords
Funding Information
- Kreftforeningen
- Canadian Institutes of Health Research
- National Institutes of Health
- American Heart Association
- Novo Nordisk Fonden
This publication has 43 references indexed in Scilit:
- Hrs regulates multivesicular body formation via ESCRT recruitment to endosomesThe Journal of cell biology, 2003
- STAM and Hrs Are Subunits of a Multivalent Ubiquitin-binding Complex on Early EndosomesPublished by Elsevier BV ,2003
- Endosome-Associated Complex, ESCRT-II, Recruits Transport Machinery for Protein Sorting at the Multivesicular BodyDevelopmental Cell, 2002
- The Vps27p–Hse1p complex binds ubiquitin and mediates endosomal protein sortingNature, 2002
- Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein–ubiquitin conjugatesThe Journal of cell biology, 2002
- TSG101/Mammalian VPS23 and Mammalian VPS28 Interact Directly and Are Recruited to VPS4-induced EndosomesJournal of Biological Chemistry, 2001
- The Doa4 Deubiquitinating Enzyme Is Functionally Linked to the Vacuolar Protein-sorting and Endocytic PathwaysMolecular Biology of the Cell, 2000
- The Vps4p AAA ATPase regulates membrane association of a Vps protein complex required for normal endosome functionThe EMBO Journal, 1998
- Endosomal transport function in yeast requires a novel AAA-type ATPase, Vps4pThe EMBO Journal, 1997
- Clathrin assembly protein AP-2 induces aggregation of membrane vesicles: a possible role for AP-2 in endosome formation.The Journal of cell biology, 1992