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TBC1D18 is a Rab5-GAP that coordinates endosome maturation together with Mon1

J Cell Biol. 2022-10; 
Shu Hiragi, Takahide Matsui, Yuriko Sakamaki, Mitsunori Fukuda
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Proteins, Expression, Isolation and Analysis … assay GAPs for purified Rabs, GST-tag of GST-Rabs were cleaved by thrombin digestion, and the cleaved GST and thrombin were removed with glutathione magnetic beads (GenScript Get A Quote

摘要

Rab5 and Rab7 are known to regulate endosome maturation, and a Rab5-to-Rab7 conversion mediated by a Rab7 activator, Mon1-Ccz1, is essential for progression of the maturation process. However, the importance and mechanism of Rab5 inactivation during endosome maturation are poorly understood. Here, we report a novel Rab5-GAP, TBC1D18, which is associated with Mon1 and mediates endosome maturation. We found that increased active Rab5 (Rab5 hyperactivation) in addition to reduced active Rab7 (Rab7 inactivation) occurs in the absence of Mon1. We present evidence showing that the severe defects in endosome maturation in Mon1-KO cells are attributable to Rab5 hyperactivation rather than to Rab7 inactivation. We then ... More

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