Rab5 activation on macropinosomes requires ALS2, and subsequent Rab5 inactivation through ALS2 detachment requires active Rab7

FEBS Letters

article

So Morishita¹  Naoyuki Wada²  Mitsunori Fukuda³  Takeshi Nakamura¹ 

[1] Division of Biosignaling, Research Institute for Biomedical Sciences, Tokyo University of Science;Department of Applied Biological Science, Tokyo University of Science;Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University

关键词: amyotrophic lateral sclerosis;    endosome;    macropinocytosis;    membrane trafficking;    Rab switch;   

DOI  :  10.1002/1873-3468.13306

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 F€orster resonance energy transfer imaging. Rab5 is activated and concurrently recruited to macropinosomes during ruffle closure. ALS2 depletion abolishes transient Rab5 activation on macropinosomes, while ALS2 is recruited to macropinosomes simultaneously with Rab5 activation. Thus, we conclude ALS2 activates Rab5 on macropinosomes. The absence of active Rab7 prolongs ALS2 presence and Rab5 activation on macropinosomes, indicating that active Rab7 is necessary for Rab5 inactivation through ALS2 dissociation and plays key roles in the Rab switch on macropinosomes.

【 授权许可】

Unknown