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ER‐plasma membrane contact sites regulate sterol import in yeast
Author(s) -
Me Anant,
Sere Yves Y.,
Johansen Jesper,
Quon Evan,
Chauhan Neha,
Beh Christopher T.
Publication year - 2016
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.30.1_supplement.115.3
Subject(s) - sterol , ergosterol , yeast , chemistry , membrane , lipid droplet , microbiology and biotechnology , saccharomyces cerevisiae , phosphatidylinositol , biophysics , biochemistry , biology , cholesterol , signal transduction
Sterols must be distributed from their site of synthesis or point of import to other cellular membranes. The high, bidirectional flux of sterol between the ER and plasma membrane (PM), ~100,000 molecules/second, occurs by non‐vesicular mechanisms involving sterol transport proteins (STPs) that may localize to ER‐PM contact sites. In wild‐type yeast cells ~48% of the PM is closely associated with ER. To test whether this association plays a role in sterol transport, we created a yeast strain, Δ‐s‐tether (based on Δtether (Manford et al. (2012) Dev Cell 23:1129)), where ER‐PM contacts were largely absent. Electron microscopy of thin sections indicated that more than a third of the Δ‐s‐tether cells examined had no detectable contacts, and that on average only 1.7% of the PM was contacted by ER. We found that whereas Δ‐s‐tether cells display high levels of PM phosphatidylinositol‐4‐phosphate and choline‐dependent growth, consistent with lack of ER‐PM contacts, the rate at which newly synthesized ergosterol exchanges with the PM was surprisingly unaffected. However, transport of exogenously supplied sterol to the ER was slowed dramatically, an effect that could be reversed by growing the cells in choline or by over‐expressing an artificial ER‐PM tethering molecule. Our results suggest that ER‐PM contact sites control a critical step in sterol import.