ALS2, the small GTPase Rab17-interacting protein, regulates maturation and sorting of Rab17-associated endosomes

Suzuka Ono, Asako Otomo, Shuji Murakoshi, Shun Mitsui, Kai Sato, Mitsunori Fukuda, Shinji Hadano

Research output: Contribution to journalArticlepeer-review

Abstract

Small GTPase Rab17 has been shown to regulate a wide range of physiological processes including cell migration in tumor cells and dendrite morphogenesis in neurons. However, molecular mechanism underlying Rab17-mediated intracellular trafficking is still unclear. To address this issue, we focused on Rab17-interacting protein ALS2, which was also known as a guanine nucleotide exchange factor (GEF) for Rab5, and investigated how ALS2 contributed to Rab17-associated membrane trafficking in cells. Rab17 was primarily localized to endosomal compartments, particularly to recycling endosomes, which was dependent on Rab11 expression. Upon Rac1 activation, Rab17 along with ALS2 was recruited to membrane ruffles and early endosomes in a Rab5 activity-independent manner. While RABGEF1, another Rab17-interacting Rab5 GEF, functioned as a GEF for Rab17, ALS2 did not possess such catalytic activity but merely interacted with Rab17. Importantly, ALS2 acted downstream of RABGEF1, regulating the maturation of Rab17-residing nascent endosomes to early endosome antigen 1 (EEA1)-positive early endosomes. Further, these Rab17-residing nascent endosomes were arisen via clathrin-independent endocytosis (CIE). Collectively, ALS2 plays a crucial role in the regulation of Rab17-associated endosomal trafficking and maturation, probably through their physical interaction, in cells.

Original languageEnglish
Pages (from-to)908-915
Number of pages8
JournalBiochemical and biophysical research communications
Volume523
Issue number4
DOIs
Publication statusPublished - 2020 Mar 19

Keywords

  • ALS2
  • Clathrin-independent endocytosis (CIE)
  • Endosome
  • RABGEF1
  • Rab17

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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