Lipid kinases VPS34 and PIKfyve coordinate a phosphoinositide cascade to regulate retriever-mediated recycling on endosomes. Academic Article uri icon

Overview

abstract

  • Cell surface receptors control how cells respond to their environment. Many cell surface receptors recycle from endosomes to the plasma membrane via a recently discovered pathway, which includes sorting-nexin SNX17, Retriever, WASH, and CCC complexes. Here, using mammalian cells, we discover that PIKfyve and its upstream PI3-kinase VPS34 positively regulate this pathway. VPS34 produces phosphatidylinositol 3-phosphate (PI3P), which is the substrate for PIKfyve to generate PI3,5P2. We show that PIKfyve controls recycling of cargoes including integrins, receptors that control cell migration. Furthermore, endogenous PIKfyve colocalizes with SNX17, Retriever, WASH, and CCC complexes on endosomes. Importantly, PIKfyve inhibition results in displacement of Retriever and CCC from endosomes. In addition, we show that recruitment of SNX17 is an early step and requires VPS34. These discoveries suggest that VPS34 and PIKfyve coordinate an ordered pathway to regulate recycling from endosomes and suggest how PIKfyve functions in cell migration.

publication date

  • January 18, 2022

Research

keywords

  • Cell Membrane
  • Endosomes
  • Phosphatidylinositol 3-Kinases
  • Phosphatidylinositols

Identity

PubMed Central ID

  • PMC8816382

Scopus Document Identifier

  • 85123623295

Digital Object Identifier (DOI)

  • 10.1073/pnas.1203106109

PubMed ID

  • 35040777

Additional Document Info

volume

  • 11