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Updated: Nov 6, 2025

The Microscopy-Based Assay to Study and Analyze the Recycling Endosomes using SNARE Trafficking
Published on: February 12, 2022
JRAB/MICAL-L2 undergoes liquid-liquid phase separation to form tubular recycling endosomes
Ayuko Sakane1,2, Taka-Aki Yano3, Takayuki Uchihashi4,5
1Department of Biochemistry, Tokushima University Graduate School of Medical Sciences, Tokushima, Japan. sakane@tokushima-u.ac.jp.
Abstract:
Elongated tubular endosomes play essential roles in diverse cellular functions. Multiple molecules have been implicated in tubulation of recycling endosomes, but the mechanism of endosomal tubule biogenesis has remained unclear. In this study, we found that JRAB/MICAL-L2 induces endosomal tubulation via activated Rab8A. In association with Rab8A, JRAB/MICAL-L2 adopts its closed form, which functions in the tubulation of recycling endosomes. Moreover, JRAB/MICAL-L2 induces liquid-liquid phase separation, initiating the formation of tubular recycling endosomes upon overexpression. Between its N-terminal and C-terminal globular domains, JRAB/MICAL-L2 contains an intrinsically disordered region, which contributes to the formation of JRAB/MICAL-L2 condensates. Based on our findings, we propose that JRAB/MICAL-L2 plays two sequential roles in the biogenesis of tubular recycling endosomes: first, JRAB/MICAL-L2 organizes phase separation, and then the closed form of JRAB/MICAL-L2 formed by interaction with Rab8A promotes endosomal tubulation.
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