Role of ORPs in Sterol Transport from Plasma Membrane to ER and Lipid Droplets in Mammalian Cells

Maurice Jansen, Yuki Ohsaki, Laura Rita Rega, Robert Bittman, Vesa M. Olkkonen, Elina Ikonen

Research output: Contribution to journalArticlepeer-review

Abstract

we investigated the mechanisms of sterol transport from the plasma membrane (PM) to the endoplasmic reticulum (ER) and lipid droplets (LDs) in HeLa cells. By overexpressing all mammalian oxysterol-binding protein-related proteins (ORPs), we found that especially ORP1S and ORP2 enhanced PM-to-LD sterol transport. This reflected the stimulation of transport from the PM to the ER, rather than from the ER to LDs. Double knockdown of ORP1S and ORP2 inhibited sterol transport from the PM to the ER and LDs, suggesting a physiological role for these ORPs in the process. A two phenylalanines in an acidic tract (FFAT) motif in ORPs that mediates interaction with VAMP-associated proteins (VAPs) in the ER was not necessary for the enhancement of sterol transport by ORPs. However, VAP-A and VAP-B silencing slowed down PM-to-LD sterol transport. This was accompanied by enhanced degradation of ORP2 and decreased levels of several FFAT motif-containing ORPs, suggesting a role for VAPs in sterol transport by stabilization of ORPs.

Original languageEnglish
Pages (from-to)218-231
Number of pages14
JournalTraffic
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2011

Keywords

  • BODIPY-cholesterol
  • Cholesterol
  • FFAT motif
  • Lipid droplet
  • Oxysterol-binding protein
  • Sterol traffic
  • VAMP-associated protein

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Structural Biology
  • Molecular Biology
  • Genetics

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