Vacuole membrane protein 1 marks endoplasmic reticulum subdomains enriched in phospholipid synthesizing enzymes and is required for phosphoinositide distribution

Traffic. 2018 Aug;19(8):624-638. doi: 10.1111/tra.12581. Epub 2018 Jun 10.

Abstract

The multispanning membrane protein vacuole membrane protein 1 (VMP1) marks and regulates endoplasmic reticulum (ER)-domains associated with diverse ER-organelle membrane contact sites. A proportion of these domains associate with endosomes during their maturation and remodeling. We found that these VMP1 domains are enriched in choline/ethanolamine phosphotransferase and phosphatidylinositol synthase (PIS1), 2 ER enzymes required for the synthesis of various phospholipids. Interestingly, the lack of VMP1 impairs the formation of PIS1-enriched ER domains, suggesting a role in the distribution of phosphoinositides. In fact, depletion of VMP1 alters the distribution of PtdIns4P and proteins involved in the trafficking of PtdIns4P. Consistently, in these conditions, defects were observed in endosome trafficking and maturation as well as in Golgi morphology. We propose that VMP1 regulates the formation of ER domains enriched in lipid synthesizing enzymes. These domains might be necessary for efficient distribution of PtdIns4P and perhaps other lipid species. These findings, along with previous reports that involved VMP1 in regulating PtdIns3P during autophagy, expand the role of VMP1 in lipid trafficking and explain the pleiotropic effects observed in VMP1-deficient mammalian cells and other model systems.

Keywords: VMP1; autophagy; lipid trafficking; membrane contact sites; phosphoinositides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / physiology
  • CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase / metabolism*
  • COS Cells
  • Cell Line
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Endoplasmic Reticulum / metabolism*
  • Endosomes / metabolism
  • Golgi Apparatus / metabolism
  • HeLa Cells
  • Humans
  • Membrane Proteins / metabolism*
  • Phosphatidylinositol Phosphates / metabolism
  • Phosphatidylinositols / metabolism*
  • Protein Transport / physiology
  • Vacuoles / metabolism*

Substances

  • Membrane Proteins
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • phosphatidylinositol 3-phosphate
  • phosphatidylinositol 4-phosphate
  • CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase