title: An unconventional diacylglycerol kinase that regulates phospholipid synthesis and nuclear membrane growth.
abstract: 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 pah1Delta cells. We propose that phosphatidate metabolism is a critical factor determining nuclear structure by regulating nuclear membrane biogenesis.
authors.affiliation: Department of Food Science and the Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901, USA.
authors.forename: Gil-Soo
authors.initials: GS
authors.lastname: Han
authors.forename: Laura
authors.initials: L
authors.lastname: O'Hara
authors.forename: George M
authors.initials: GM
authors.lastname: Carman
authors.forename: Symeon
authors.initials: S
authors.lastname: Siniossoglou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003570:Cytidine Triphosphate / Q000378:metabolism; D019852:Diacylglycerol Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000378:metabolism*; D010743:Phospholipids / Q000096:biosynthesis*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D010743:Phospholipids; D003570:Cytidine Triphosphate; D019852:Diacylglycerol Kinase