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Oxysterol‐ and cholesterol‐dependent translocation of CTP:phosphocholine Cytidylyltransferase to the nuclear envelope
Author(s) -
Gehrig Karsten,
Lagace Thomas A,
Ridgway Neale D
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.643.4
Subject(s) - phosphocholine , oxysterol , phosphatidylcholine , sphingomyelin , sterol , choline , chemistry , cholesterol , vesicle , phospholipid , sterol regulatory element binding protein , biochemistry , microbiology and biotechnology , choline kinase , biology , membrane
Oxysterols potently regulate cholesterol, phospholipid and sphingomyelin synthesis. Here, we investigated how 22‐, 25‐, and 26‐hydroxycholesterol (22OH, 25OH, and 26OH, respectively) stimulate the CDP‐choline pathway for phosphatidylcholine (PtdCho) synthesis using CHOK1 and CHO cells that express a sterol‐resistant mutant of sterol regulatory element binding‐protein (SREBP)‐cleavage activating protein (CHOSCAP D443N). Analysis of [3H]choline‐labelled metabolites showed that oxysterols activated CTP:phosphocholine cytidylyltransferase (CCTα) and increased PtdCho synthesis. Oxysterols also promoted complete localization of CCTα to the nuclear envelope and intranuclear tubules in both CHO‐SCAP D443N and CHOK1 cells. Cholesterol was required for this effect since depletion with cyclodextrin or lovastatin resulted in reduced translocation and activation of PtdCho synthesis. In vitro , CCTα activity was stimulated by PtdCho vesicles containing oxysterols. Synergistic activation of CCTα by vesicles with 25OH and cholesterol suggested that the membrane environment created by the combination of these two sterols has unique stimulatory properties that could be reproduced in CHO‐SCAP‐D443N cells. Thus 22, 25, and 26‐OH promotes translocation and activation of CCTα at the nuclear envelope in a cholesterol‐dependent manner. (Supported by CIHR and IWK)