Golgi localization of oxysterol binding protein-related protein 4L (ORP4L) is regulated by ligand binding

J Cell Sci. 2018 Jul 19;131(14):jcs215335. doi: 10.1242/jcs.215335.


Oxysterol binding protein (OSBP)-related protein 4L (ORP4L, also known as OSBPL2), a closely related paralogue and interacting partner of OSBP, binds sterols and phosphatidylinositol 4-phosphate [PI(4)P] and regulates cell proliferative signalling at the plasma membrane (PM). Here, we report that ORP4L also interacts with the trans-Golgi network (TGN) in an OSBP-, sterol- and PI(4)P-dependent manner. Characterization of ORP4L lipid and VAP binding mutants indicated an indirect mechanism for translocation to ER-Golgi contact sites in response to 25-hydroxycholesterol that was dependent on OSBP and PI(4)P. shRNA silencing revealed that ORP4L was required to maintain the organization and PI(4)P content of the Golgi and TGN. In contrast, the interaction of ORP4L with the PM was not dependent on its sterol, PI(4)P or VAP binding activities. At the PM, ORP4L partially localized with a genetically encoded probe for PI(4)P but not with a probe for phosphatidylinositol 4,5-bisphosphate. We conclude that ORP4L is differentially localized to the PM and ER-Golgi contacts sites. OSBP-, lipid- and VAP-regulated interactions of ORP4L with ER-Golgi contact sites are involved in the maintenance of Golgi and TGN structure.

Keywords: Golgi complex; Membrane contact sites; Oxysterol binding proteins; Phosphatidylinositol 4-phosphate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism
  • Golgi Apparatus / genetics
  • Golgi Apparatus / metabolism*
  • Humans
  • Hydroxycholesterols / metabolism
  • Ligands
  • Phosphatidylinositol Phosphates / metabolism*
  • Protein Binding
  • Protein Transport
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism*
  • Sterols / metabolism*


  • Hydroxycholesterols
  • Ligands
  • Phosphatidylinositol Phosphates
  • Receptors, Steroid
  • Sterols
  • oxysterol binding protein
  • phosphatidylinositol 4-phosphate
  • 25-hydroxycholesterol

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