title: Plasma membrane--endoplasmic reticulum contact sites regulate phosphatidylcholine synthesis.
abstract: Synthesis of phospholipids, sterols and sphingolipids is thought to occur at contact sites between the endoplasmic reticulum (ER) and other organelles because many lipid-synthesizing enzymes are enriched in these contacts. In only a few cases have the enzymes been localized to contacts in vivo and in no instances have the contacts been demonstrated to be required for enzyme function. Here, we show that plasma membrane (PM)--ER contact sites in yeast are required for phosphatidylcholine synthesis and regulate the activity of the phosphatidylethanolamine N-methyltransferase enzyme, Opi3. Opi3 activity requires Osh3, which localizes to PM-ER contacts where it might facilitate in trans catalysis by Opi3. Thus, membrane contact sites provide a structural mechanism to regulate lipid synthesis.
authors.affiliation: Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Tavassoli
authors.forename: Jesse T
authors.initials: JT
authors.lastname: Chao
authors.forename: Barry P
authors.initials: BP
authors.lastname: Young
authors.forename: Ruud C
authors.initials: RC
authors.lastname: Cox
authors.forename: William A
authors.initials: WA
authors.lastname: Prinz
authors.forename: Anton I P M
authors.initials: AI
authors.lastname: de Kroon
authors.forename: Christopher J R
authors.initials: CJ
authors.lastname: Loewen
mesh_terms: D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D055786:Gene Knockout Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010711:Phosphatidate Phosphatase / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C500973:Ice2 protein, S cerevisiae; D008565:Membrane Proteins; D010713:Phosphatidylcholines; D029701:Saccharomyces cerevisiae Proteins; C501314:Scs2 protein, S cerevisiae; C081864:SAC1 protein, S cerevisiae; D010744:Phosphoric Monoester Hydrolases; C079831:PAH1 protein, S cerevisiae; D010711:Phosphatidate Phosphatase