Rubicon controls endosome maturation as a Rab7 effector

作者: Q. Sun , W. Westphal , K. N. Wong , I. Tan , Q. Zhong

DOI: 10.1073/PNAS.1010554107

关键词: Endocytic cycleEffectorGuanine nucleotide exchange factorUVRAGEndosomeBiologyGTPaseCell biologySmall GTPaseLate endosome

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

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