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JRAB/MICAL-L2 通过液-液相分离形成管状再循环内体。

JRAB/MICAL-L2 undergoes liquid-liquid phase separation to form tubular recycling endosomes.

机构信息

Department of Biochemistry, Tokushima University Graduate School of Medical Sciences, Tokushima, Japan.

Department of Interdisciplinary Researches for Medicine and Photonics, Institute of Post-LED Photonics, Tokushima, Japan.

出版信息

Commun Biol. 2021 May 11;4(1):551. doi: 10.1038/s42003-021-02080-7.

DOI:10.1038/s42003-021-02080-7
PMID:33976349
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8113518/
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.

摘要

伸长的管状内体在多种细胞功能中发挥着重要作用。多种分子已被牵连到再循环内体的小管化中，但内体小管发生的机制仍不清楚。在这项研究中，我们发现 JRAB/MICAL-L2 通过激活 Rab8A 诱导内体小管化。与 Rab8A 结合后，JRAB/MICAL-L2 采用其封闭形式，在再循环内体的小管化中发挥作用。此外，JRAB/MICAL-L2 诱导液-液相分离，在过表达时引发管状再循环内体的形成。在其 N 端和 C 端球状结构域之间，JRAB/MICAL-L2 含有一个固有无序区，有助于 JRAB/MICAL-L2 凝聚体的形成。根据我们的发现，我们提出 JRAB/MICAL-L2 在管状再循环内体发生过程中发挥两个连续的作用：首先，JRAB/MICAL-L2 组织相分离，然后与 Rab8A 相互作用形成的 JRAB/MICAL-L2 封闭形式促进内体小管化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/e5e603597877/42003_2021_2080_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/cb5018d3d2b9/42003_2021_2080_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/03d767928ec5/42003_2021_2080_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/3d0ffca9b70f/42003_2021_2080_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/376e72bf88c6/42003_2021_2080_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/b696cd03b143/42003_2021_2080_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/187f06c9a217/42003_2021_2080_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/e5e603597877/42003_2021_2080_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/cb5018d3d2b9/42003_2021_2080_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/03d767928ec5/42003_2021_2080_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/3d0ffca9b70f/42003_2021_2080_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/376e72bf88c6/42003_2021_2080_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/b696cd03b143/42003_2021_2080_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/187f06c9a217/42003_2021_2080_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132c/8113518/e5e603597877/42003_2021_2080_Fig7_HTML.jpg

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