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J. Biol. Chem., Vol. 283, Issue 29, 20433-20442, July 18, 2008

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An Unconventional Diacylglycerol Kinase That Regulates Phospholipid Synthesis and Nuclear Membrane Growth^*

Gil-Soo Han¹, Laura O'Hara¹, George M. Carman, and Symeon Siniossoglou²

From the Department of Food Science and the Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey 08901 and the Cambridge Institute for Medical Research, University of Cambridge, Hills Road, CB2 0XY Cambridge, United Kingdom

Changes in nuclear size and shape during the cell cycle or during development require coordinated nuclear membrane remodeling, but the underlying molecular events are largely unknown. We have shown previously that the activity of the conserved phosphatidate phosphatase Pah1p/Smp2p regulates nuclear structure in yeast by controlling phospholipid synthesis and membrane biogenesis at the nuclear envelope. Two screens for novel regulators of phosphatidate led to the identification of DGK1. We show that Dgk1p is a unique diacylglycerol kinase that uses CTP, instead of ATP, to generate phosphatidate. DGK1 counteracts the activity of PAH1 at the nuclear envelope by controlling phosphatidate levels. Overexpression of DGK1 causes the appearance of phosphatidate-enriched membranes around the nucleus and leads to its expansion, without proliferating the cortical endoplasmic reticulum membrane. Mutations that decrease phosphatidate levels decrease nuclear membrane growth in pah1 cells. We propose that phosphatidate metabolism is a critical factor determining nuclear structure by regulating nuclear membrane biogenesis.

Received for publication, April 15, 2008

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^* This work was supported, in whole or in part, by National Institutes of Health Grant GM-28140 from the United States Public Health Service (to G. M. C.). This work was also supported by a Wellcome Trust Career Development Fellowship in Basic Biomedical Science (to S. S). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

This article was selected as a Paper of the Week.

¹ Both authors contributed equally to this work.

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² To whom correspondence should be addressed: Cambridge Inst. for Medical Research, University of Cambridge, Wellcome Trust/MRC Bldg., Hills Rd., CB2 0XY Cambridge, UK. Tel.: 44-1223-762-641; E-mail: ss560{at}cam.ac.uk.

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This article has been cited by other articles:

				G. M. Carman and G.-S. Han Regulation of phospholipid synthesis in yeast J. Lipid Res., April 1, 2009; 50(Supplement): S69 - S73. [Abstract] [Full Text] [PDF]

				G. M. Carman and G.-S. Han Phosphatidic Acid Phosphatase, a Key Enzyme in the Regulation of Lipid Synthesis J. Biol. Chem., January 30, 2009; 284(5): 2593 - 2597. [Full Text] [PDF]

				G.-S. Han, L. O'Hara, S. Siniossoglou, and G. M. Carman Characterization of the Yeast DGK1-encoded CTP-dependent Diacylglycerol Kinase J. Biol. Chem., July 18, 2008; 283(29): 20443 - 20453. [Abstract] [Full Text] [PDF]