A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion. Academic Article uri icon

Overview

abstract

  • Exosomes are secreted to the extracellular milieu when multivesicular endosomes (MVEs) dock and fuse with the plasma membrane. However, MVEs are also known to fuse with lysosomes for degradation. How MVEs are directed to the plasma membrane for exosome secretion rather than to lysosomes is unclear. Here we report that a conversion of phosphatidylinositol-3-phosphate (PI(3)P) to phosphatidylinositol-4-phosphate (PI(4)P) catalyzed sequentially by Myotubularin 1 (MTM1) and phosphatidylinositol 4-kinase type IIα (PI4KIIα) on the surface of MVEs mediates the recruitment of the exocyst complex. The exocyst then targets the MVEs to the plasma membrane for exosome secretion. We further demonstrate that disrupting PI(4)P generation or exocyst function blocked exosomal secretion of Programmed death-ligand 1 (PD-L1), a key immune checkpoint protein in tumor cells, and led to its accumulation in lysosomes. Together, our study suggests that the PI(3)P to PI(4)P conversion on MVEs and the recruitment of the exocyst direct the exocytic trafficking of MVEs for exosome secretion.

authors

  • Liu, Diao
  • Tao, Kai
  • Wu, Bin
  • Yu, Ziyan
  • Szczepaniak, Malwina
  • Rames, Matthew
  • Yang, Changsong
  • Svitkina, Tatyana
  • Zhu, Yueyao
  • Xu, Fengyuan
  • Nan, Xiaolin
  • Guo, Wei

publication date

  • October 28, 2023

Research

keywords

  • Exosomes

Identity

PubMed Central ID

  • PMC10613218

Scopus Document Identifier

  • 85175165201

Digital Object Identifier (DOI)

  • 10.1038/s41467-023-42661-0

PubMed ID

  • 37898620

Additional Document Info

volume

  • 14

issue

  • 1