TY - JOUR
T1 - JRAB/MICAL-L2 undergoes liquid–liquid phase separation to form tubular recycling endosomes
AU - Sakane, Ayuko
AU - Yano, Taka aki
AU - Uchihashi, Takayuki
AU - Horikawa, Kazuki
AU - Hara, Yusuke
AU - Imoto, Issei
AU - Kurisu, Shusaku
AU - Yamada, Hiroshi
AU - Takei, Kohji
AU - Sasaki, Takuya
N1 - Funding Information:
We thank C. Takida (our laboratory) for technical assistance and M. Kakita (Research Administration Section, Tokushima University) for administrative assistance. The sample preparation for immunoelectron microscopic analysis was supported by Okayama University Central Research Laboratory. We also thank Drs T. Fujimoto (Juntendo University), S. Yoshizawa (RIKEN), and Y. Morishita (RIKEN) for helpful discussion and advice. This work was mainly supported by JSPS KAKENHI Grant Numbers 17K08636 (A.S.), 18H01837, 19H03225, and 19H05389 (T.U.); Takeda Science Foundation (A.S.); Osaka Foundation for Promotion of Fundamental Medical Research (A.S.); JST Moonshot R&D Grant Number JPMJMS2025 (A.S.), and the Research Cluster program of Tokushima University (T.S., A.S.; organizer, T. Katagiri).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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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U2 - 10.1038/s42003-021-02080-7
DO - 10.1038/s42003-021-02080-7
M3 - Article
C2 - 33976349
AN - SCOPUS:85105772042
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 551
ER -