Rubicon controls endosome maturation as a Rab7 effector

Qiming Sun, Wiebke Westphal, Kwun Ngok Wong, Irena Tan, Qing Zhong

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)19338-19343
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number45
DOIs
StatePublished - Nov 9 2010

Keywords

  • Autophagosome
  • Autophagy
  • Barkor/Atg14(L)
  • Endocytosis
  • Epidermal growth factor

ASJC Scopus subject areas

  • General

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