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Rab5 activation on macropinosomes requires ALS 2, and subsequent Rab5 inactivation through ALS 2 detachment requires active Rab7
Author(s) -
Morishita So,
Wada Naoyuki,
Fukuda Mitsunori,
Nakamura Takeshi
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13306
Subject(s) - rab , pinocytosis , endosome , chemistry , microbiology and biotechnology , extracellular , endocytosis , cell , biochemistry , biology , gtpase
Macropinocytosis is a nonspecific bulk uptake of extracellular fluid. During endosome maturation, the Rab5‐to‐Rab7 switch machinery executes the conversion from early to late endosomes. However, how the Rab switch works during macropinosome maturation remains unclear. Here, we elucidate the Rab switch machinery in macropinosome maturation using Förster resonance energy transfer imaging. Rab5 is activated and concurrently recruited to macropinosomes during ruffle closure. ALS 2 depletion abolishes transient Rab5 activation on macropinosomes, while ALS 2 is recruited to macropinosomes simultaneously with Rab5 activation. Thus, we conclude ALS 2 activates Rab5 on macropinosomes. The absence of active Rab7 prolongs ALS 2 presence and Rab5 activation on macropinosomes, indicating that active Rab7 is necessary for Rab5 inactivation through ALS 2 dissociation and plays key roles in the Rab switch on macropinosomes.