Han Gil-Soo, O'Hara Laura, Carman George M, Siniossoglou Symeon
Department of Food Science and the Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901, USA.
J Biol Chem. 2008 Jul 18;283(29):20433-42. doi: 10.1074/jbc.M802903200. Epub 2008 May 5.
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.
细胞周期或发育过程中核大小和形状的变化需要协调的核膜重塑，但其潜在的分子事件在很大程度上尚不清楚。我们之前已经表明，保守的磷脂酸磷酸酶Pah1p/Smp2p的活性通过控制核膜处的磷脂合成和膜生物发生来调节酵母中的核结构。对磷脂酸新调节因子的两次筛选导致了DGK1的鉴定。我们表明，Dgk1p是一种独特的二酰基甘油激酶，它使用CTP而非ATP来生成磷脂酸。DGK1通过控制磷脂酸水平来抵消PAH1在核膜处的活性。DGK1的过表达导致细胞核周围出现富含磷脂酸的膜，并导致细胞核扩张，而不使皮质内质网膜增殖。降低磷脂酸水平的突变会减少pah1Delta细胞中的核膜生长。我们提出，磷脂酸代谢是通过调节核膜生物发生来决定核结构的关键因素。
