title: Cell growth-dependent coordination of lipid signaling and glycosylation is mediated by interactions between Sac1p and Dpm1p.
abstract: The integral membrane lipid phosphatase Sac1p regulates local pools of phosphatidylinositol-4-phosphate (PtdIns(4)P) at endoplasmic reticulum (ER) and Golgi membranes. PtdIns(4)P is important for Golgi trafficking, yet the significance of PtdIns(4)P for ER function is unknown. It also remains unknown how localization of Sac1p to distinct organellar membranes is mediated. Here, we show that a COOH-terminal region in yeast Sac1p is crucial for ER targeting by directly interacting with dolicholphosphate mannose synthase Dpm1p. The interaction with Dpm1p persists during exponential cell division but is rapidly abolished when cell growth slows because of nutrient limitation, causing translocation of Sac1p to Golgi membranes. Cell growth-dependent shuttling of Sac1p between the ER and the Golgi is important for reciprocal control of PtdIns(4)P levels at these organelles. The fraction of Sac1p resident at the ER is also required for efficient dolichol oligosaccharide biosynthesis. Thus, the lipid phosphatase Sac1p may be a key regulator, coordinating the secretory capacity of ER and Golgi membranes in response to growth conditions.
authors.affiliation: Division of Nephrology and Hypertension, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Faulhammer
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Konrad
authors.forename: Ben
authors.initials: B
authors.lastname: Brankatschk
authors.forename: Sabina
authors.initials: S
authors.lastname: Tahirovic
authors.forename: Andreas
authors.initials: A
authors.lastname: Knödler
authors.forename: Peter
authors.initials: P
authors.lastname: Mayinger
mesh_terms: D015153:Blotting, Western; D043402:Cathepsin A / Q000378:metabolism; D002455:Cell Division; D002499:Centrifugation, Density Gradient; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000032:analysis; D006360:Heat-Shock Proteins / Q000032:analysis; D007425:Intracellular Membranes / Q000737:chemistry; D008358:Mannose / Q000378:metabolism; D008364:Mannosyltransferases / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000032:analysis / Q000235:genetics; D008856:Microscopy, Fluorescence; D008861:Microsomes / Q000737:chemistry; D009154:Mutation; D009844:Oligosaccharides / Q000096:biosynthesis; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases; D021381:Protein Transport / Q000502:physiology*; D000069816:SEC Translocation Channels; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017384:Sequence Deletion; D015398:Signal Transduction / Q000502:physiology*; D014170:Transformation, Genetic; D033921:Vesicular Transport Proteins / Q000032:analysis
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009844:Oligosaccharides; C087335:PEP1 protein, S cerevisiae; D018129:Phosphatidylinositol Phosphates; D000069816:SEC Translocation Channels; C499383:SEC61 protein, S cerevisiae; C074213:SEC62 protein, S cerevisiae; C074215:SEC63 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C066755:Sec7 guanine nucleotide exchange factors; D033921:Vesicular Transport Proteins; C037178:phosphatidylinositol 4-phosphate; D049452:Green Fluorescent Proteins; D008364:Mannosyltransferases; C022755:dolichyl-phosphate beta-D-mannosyltransferase; C081864:SAC1 protein, S cerevisiae; D010744:Phosphoric Monoester Hydrolases; D043402:Cathepsin A; D005947:Glucose; D008358:Mannose