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PMID: 20974968 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Rubicon controls endosome maturation as a Rab7 effector.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 107 ·No. 45 ·2010-11-09 ·Pages 19338-43

Sun Q, Westphal W, Wong KN, Tan I, Zhong Q

Abstract

The activation and recruitment of the small GTPase Rab7 to early endosome is a critical step for early to late endosome maturation, a process that requires the class III phosphatidylinositol 3-kinase (PI3KC3) and GTPase regulators. However, the molecular mechanism underlying Rab7 activation and endosome maturation is still poorly defined. Here we report that Rubicon, a component of the PI3KC3 complex, prevents endosome maturation through differential interactions with Rab7 and UVRAG. UVRAG activates PI3KC3 and C-VPS/HOPS, a guanine nucleotide exchange factor that catalyzes the exchange of GDP for GTP on Rab7. We demonstrate that Rubicon sequesters UVRAG from C-VPS/HOPS. Active GTP-bound Rab7 competes for Rubicon binding and releases UVRAG to associate with C-VPS/HOPS, which in turn promotes further loading of Rab7 with GTP. This feed-forward loop ensures rapid amplification of GTP-bound Rab7 and consequent stimulation of endosome maturation. Hence, Rubicon serves as a previously unknown Rab7 effector to ensure the proper progression of the endocytic pathway.

MeSH Terms
Autophagy-Related Proteins Carrier Proteins/metabolism Endocytosis Endosomes/metabolism Guanine Nucleotide Exchange Factors/metabolism Humans Intracellular Signaling Peptides and Proteins/physiology Phosphatidylinositol 3-Kinase/metabolism Protein Transport Tumor Suppressor Proteins/metabolism rab GTP-Binding Proteins/metabolism rab7 GTP-Binding Proteins
Chemicals
Autophagy-Related Proteins Carrier Proteins Guanine Nucleotide Exchange Factors Intracellular Signaling Peptides and Proteins RUBCN protein, human Tumor Suppressor Proteins UVRAG protein, human rab7 GTP-Binding Proteins rab7 GTP-binding proteins, human Phosphatidylinositol 3-Kinase rab GTP-Binding Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sun Qiming
Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Westphal Wiebke
Wong Kwun Ngok
Tan Irena
Zhong Qing
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1010554107
Published
2010-11-09
Epub
2010-00-25
Pages
19338-43
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2984168
Subset
IM
Grants
NCI NIH HHS · R01 CA133228 · United States
External Links
PubMed source DOI: 10.1073/pnas.1010554107 PMC Full Text View journal details
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