Diacylglycerol at the inner nuclear membrane fuels nuclear envelope expansion in closed mitosis

被引:16
作者
Foo, Sherman [1 ,2 ]
Cazenave-Gassiot, Amaury [3 ,4 ]
Wenk, Markus R. [3 ,4 ]
Oliferenko, Snezhana [1 ,2 ]
机构
[1] Francis Crick Inst, 1 Midland Rd, London NW1 1AT, England
[2] Kings Coll London, Randall Ctr Cell & Mol Biophys, Sch Basic & Med Biosci, London SE1 1UL, England
[3] Natl Univ Singapore, Life Sci Inst, Dept Biochem, Singapore Lipid Incubator,Yong Loo Lin Sch Med, MD7, 8 Med Dr, Singapore 117596, Singapore
[4] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Precis Med Translat Res Program, MD7, 8 Med Dr, Singapore 117596, Singapore
基金
英国生物技术与生命科学研究理事会;
关键词
Closed mitosis; Diacylglycerol; Nuclear envelope; PHOSPHATIDIC-ACID; FUNCTIONAL GENOMICS; GENE-EXPRESSION; FISSION YEAST; EFFICIENT; BIOSYNTHESIS; STRATEGIES; PATHWAY; KINASE; SHAPE;
D O I
10.1242/jcs.260568
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Nuclear envelope (NE) expansion must be controlled to maintain nuclear shape and function. The nuclear membrane expands massively during closed mitosis, enabling chromosome segregation within an intact NE. Phosphatidic acid (PA) and diacylglycerol (DG) can both serve as biosynthetic precursors for membrane lipid synthesis. How they are regulated in time and space and what the implications are of changes in their flux for mitotic fidelity are largely unknown. Using genetically encoded PA and DG probes, we show that DG is depleted from the inner nuclear membrane during mitosis in the fission yeast Schizosaccharomyces pombe, but PA does not accumulate, indicating that it is rerouted to membrane synthesis. We demonstrate that DG-to-PA conversion catalyzed by the diacylglycerol kinase Dgk1 (also known as Ptp4) and direct glycerophospholipid synthesis from DG by diacylglycerol cholinephosphotransferase/ ethanolaminephosphotransferase Ept1 reinforce NE expansion. We conclude that DG consumption through both the de novo pathway and the Kennedy pathway fuels a spike in glycerophospholipid biosynthesis, controlling NE expansion and, ultimately, mitotic fidelity.
引用
收藏
页数:14
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