Nucleocytoplasmic shuttling of the Golgi phosphatidylinositol 4-kinase Pik1 is regulated by 14-3-3 proteins and coordinates Golgi function with cell growth

• Published in: Molecular biology of the cell Vol. 19; no. 3; pp. 1046 - 1061
• Main Authors: Demmel, Lars, Beck, Mike, Klose, Christian, Schlaitz, Anne-Lore, Gloor, Yvonne, Hsu, Peggy P, Havlis, Jan, Shevchenko, Andrej, Krause, Eberhard, Kalaidzidis, Yannis, Walch-Solimena, Christiane
• Format: Journal Article
• Language: English
• Published: United States The American Society for Cell Biology 01.03.2008
• Subjects: 1-Phosphatidylinositol 4-Kinase - chemistry; 1-Phosphatidylinositol 4-Kinase - metabolism; 14-3-3 Proteins - metabolism; Active Transport, Cell Nucleus; Amino Acid Sequence; Cell Nucleus - enzymology; Cell Proliferation; Food; Golgi Apparatus - enzymology; Models, Biological; Molecular Sequence Data; Multiprotein Complexes - metabolism; Mutation - genetics; Phosphorylation; Phosphoserine - metabolism; Protein Binding; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - metabolism; trans-Golgi Network - enzymology
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E07-02-0134

The yeast phosphatidylinositol 4-kinase Pik1p is essential for proliferation, and it controls Golgi homeostasis and transport of newly synthesized proteins from this compartment. At the Golgi, phosphatidylinositol 4-phosphate recruits multiple cytosolic effectors involved in formation of post-Golgi transport vesicles. A second pool of catalytically active Pik1p localizes to the nucleus. The physiological significance and regulation of this dual localization of the lipid kinase remains unknown. Here, we show that Pik1p binds to the redundant 14-3-3 proteins Bmh1p and Bmh2p. We provide evidence that nucleocytoplasmic shuttling of Pik1p involves phosphorylation and that 14-3-3 proteins bind Pik1p in the cytoplasm. Nutrient deprivation results in relocation of Pik1p from the Golgi to the nucleus and increases the amount of Pik1p-14-3-3 complex, a process reversed upon restored nutrient supply. These data suggest a role of Pik1p nucleocytoplasmic shuttling in coordination of biosynthetic transport from the Golgi with nutrient signaling.