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Originally published as MBC in Press, 10.1091/mbc.E07-02-0134 on January 2, 2008

Vol. 19, Issue 3, 1046-1061, March 2008

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Nucleocytoplasmic Shuttling of the Golgi Phosphatidylinositol 4-Kinase Pik1 Is Regulated by 14-3-3 Proteins and Coordinates Golgi Function with Cell Growth

Lars Demmel*,{dagger}, Mike Beck*,{dagger}, Christian Klose{dagger}, Anne-Lore Schlaitz{dagger}, Yvonne Gloor{dagger}, Peggy P. Hsu{ddagger}, Jan Havlis{dagger},§, Andrej Shevchenko{dagger}, Eberhard Krause||, Yannis Kalaidzidis{dagger}, and Christiane Walch-Solimena{dagger}

{dagger}Max Planck Institute of Molecular Cell Biology and Genetics, Dresden D-01307, Germany; {ddagger}Whitehead Institute for Biomedical Research, Cambridge, MA 02142; ||Mass Spectrometry Group, Leibniz Institute of Molecular Pharmacology, Berlin D-13125, Germany; and A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119899, Russia

Submitted February 16, 2007; Revised December 13, 2007; Accepted December 20, 2007
Monitoring Editor: Benjamin Glick

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.


This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-02-0134) on January 2, 2008.

* These authors contributed equally to this work.

Present address: § Faculty of Science, Department of Analytical Chemistry, Masaryk University, Brno, Czech Republic.

Address correspondence to: Christiane Walch-Solimena (csolimena{at}mpi-cbg.de)

Abbreviations used: ASR, arrest of secretion response; {lambda}-PPase, {lambda}-protein phosphatase; GST, Glutathione S-transferase; PAP, peroxidase anti-peroxidase; PI, phosphoinositide; PI 4-kinase, phosphatidylinositol 4-kinase; PI(4)P, phosphatidylinositol 4-phosphate; TGN, trans-Golgi network; TAP, tandem affinity purification.




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