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Oxysterol binding protein‐related protein 9 is required for Golgi organization and secretion
Author(s) -
Ngo Michael H,
Ridgway Neale
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.805.7
Subject(s) - golgi apparatus , pleckstrin homology domain , microbiology and biotechnology , biology , secretory pathway , secretion , sphingomyelin , transport protein , phosphatidylinositol , signal transduction , biochemistry , endoplasmic reticulum , membrane
Oxysterol binding protein (OSBP)‐related protein 9 (ORP9) is a member of the OSBP gene family implicated in ER/Golgi transport and lipid regulation. Due to alternate promoter start sites, ORP9 is expressed as a full length (ORP9L) and N‐terminal truncated variant (ORP9S). ORP9L localizes to the trans‐Golgi via pleckstrin homology (PH) domain by interaction with phosphatidylinositol‐4‐phosphate (PI‐4P). ORP9L and ORP9S also localize to ER compartments by interaction with vesicle associated‐membrane protein (VAMP)‐associated protein (VAP). Overexpression of ORP9L in CHO cells had no effect on growth, however overexpression of ORP9S caused significant inhibition. Growth inhibition appeared to be related to a seccretory defect. Enforced overexpression of ORP9S and ORP9L depletion by RNAi experiments resulted in fragmentation of the cis and trans elements of the Golgi. VSVG trafficking through the Golgi, measured by an endoH sensitivity, was disrupted by ORP9S expression and ORP9L depletion. Altered expression of ORP9S and ORP9L had no effect on 25‐hydroxycholesterol activated synthesis of sphingomyelin, suggesting that ORP9 does not have a role in OSBP regulation of CERT recruitment to the Golgi. These results indicate that ORP9L plays an important role in maintaining Golgi structure and secretion by interacting with PI‐4P, and ORP9S is a dominant negative regulator of ORP9L.