Growth control of Golgi phosphoinositides by reciprocal localization of sac1 lipid phosphatase and pik1 4-kinase.
Compartment-specific control of phosphoinositide lipids is essential for cell function. The Sac1 lipid phosphatase regulates endoplasmic reticulum (ER) and Golgi phosphatidylinositol-4-phosphate [PI(4)P] in response to nutrient levels and cell growth stages. During exponential growth, Sac1p interacts with Dpm1p at the ER but shuttles to the Golgi during starvation. Here, we report that a C-terminal region in Sac1p is required for retention in the perinuclear ER, whereas the N-terminal domain is responsible for Golgi localization. We also show that starvation-induced shuttling of Sac1p to the Golgi depends on the coat protein complex II and the Rer1 adaptor protein. Starvation-induced shuttling of Sac1p to the Golgi specifically eliminates a pool of PI(4)P generated by the lipid kinase Pik1p. In addition, absence of nutrients leads to a rapid dissociation of Pik1p, together with its non-catalytical subunit Frq1p, from Golgi membranes. Reciprocal rounds of association/dissociation of the Sac1p lipid phosphatase and the Pik1p/Frq1p lipid kinase complex are responsible for growth-dependent control of Golgi phosphoinositides. Sac1p and Pik1p/Frq1p are therefore elements of a unique machinery that synchronizes ER and Golgi function in response to different growth conditions.
Faulhammer
Frank
F
Department of Medicine, Division of Nephrology and Hypertension, Oregon Health and Science University, Portland, OR 97239, USA.
Kanjilal-Kolar
Suparna
S
Knödler
Andreas
A
Lo
Jennifer
J
Lee
Yerim
Y
Konrad
Gerlinde
G
Mayinger
Peter
P
D019870:1-Phosphatidylinositol 4-Kinase / Q000502:physiology*; D020816:Amino Acid Motifs; D001692:Biological Transport; D003432:Cross-Linking Reagents / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D006056:Golgi Apparatus / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000378:metabolism; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D016296:Mutagenesis; D010716:Phosphatidylinositols / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*
D003432:Cross-Linking Reagents; D010716:Phosphatidylinositols; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; D019870:1-Phosphatidylinositol 4-Kinase; C441760:PIK1 protein, S cerevisiae; C081864:SAC1 protein, S cerevisiae; D010744:Phosphoric Monoester Hydrolases