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Oxysterol‐binding protein recruitment and activity at the endoplasmic reticulum‐Golgi interface are independent of Sac1
Author(s) -
Charman Mark,
Goto Asako,
Ridgway Neale D.
Publication year - 2017
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12491
Subject(s) - golgi apparatus , endoplasmic reticulum , microbiology and biotechnology , biology , pleckstrin homology domain , copii , secretory pathway , phosphorylation
Oxysterol‐binding protein ( OSBP ) localizes to endoplasmic reticulum ( ER )‐Golgi contact sites where it transports cholesterol and phosphatidylinositol 4‐phosphate ( PI‐4P ), and activates lipid transport and biosynthetic activities. The PI‐4P phosphatase Sac1 cycles between the ER and Golgi apparatus where it potentially regulates OSBP activity. Here we examined whether the ER ‐Golgi distribution of endogenous or ectopically expressed Sac1 influences OSBP activity. OSBP and Sac1 co‐localized at apparent ER ‐Golgi contact sites in response to 25‐hydroxycholesterol ( 25OH ), cholesterol depletion and p38 MAPK inhibitors. A Sac1 mutant that is unable to exit the ER did not localize with OSBP , suggesting that sterol perturbations cause Sac1 transport to the Golgi apparatus. Ectopic expression of Sac1 in the ER or Golgi apparatus, or Sac1 silencing, did not affect OSBP localization to ER ‐Golgi contact sites, OSBP ‐dependent activation of sphingomyelin synthesis, or cholesterol esterification in the ER . p38 MAPK inhibition and retention of Sac1 in the Golgi apparatus also caused OSBP phosphorylation and OSBP ‐dependent activation of sphingomyelin synthesis at ER ‐Golgi contacts. These results demonstrate that Sac1 expression in either the ER or Golgi apparatus has a minimal impact on the PI‐4P that regulates OSBP activity or recruitment to contact sites.