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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytoskeletal Proteins / metabolism
  • Endocytosis / physiology
  • Endosomes / metabolism*
  • Endosomes / physiology
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Microfilament Proteins / metabolism*
  • Microfilament Proteins / physiology
  • Protein Binding / physiology
  • Protein Transport / physiology
  • Tight Junctions / physiology
  • rab GTP-Binding Proteins / metabolism
  • rab GTP-Binding Proteins / physiology

Substances

  • Cytoskeletal Proteins
  • MICALL2 protein, human
  • Microfilament Proteins
  • RAB8A protein, human
  • rab GTP-Binding Proteins