Open AccessGolgi- localization of oxysterol binding protein-related protein 4L (ORP4L) is regulated by ligand binding
Author(s) -
Antonietta Pietrangelo,
Neale D. Ridgway
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.215335
Subject(s) - biology , golgi apparatus , oxysterol , plasma protein binding , ligand (biochemistry) , microbiology and biotechnology , biochemistry , receptor , endoplasmic reticulum , cholesterol
Oxysterol binding protein (OSBP)-related protein 4L (ORP4L), a closely related paralogue and interacting partner of OSBP, binds sterols and phosphatidylinositol 4-phosphate (PI(4)P) and regulates cell proliferative signaling 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 OSBP- and PI(4)P-dependent. 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/TGN structure.