Foo Sherman, Cazenave-Gassiot Amaury, Wenk Markus R, Oliferenko Snezhana
The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Randall Centre for Cell and Molecular Biophysics, School of Basic and Medical Biosciences, King's College London, London SE1 1UL, UK.
J Cell Sci. 2023 Feb 1;136(3). doi: 10.1242/jcs.260568. Epub 2023 Feb 2.
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.
必须控制核膜(NE)的扩张以维持细胞核的形态和功能。在封闭有丝分裂期间,核膜会大量扩张,使染色体能在完整的核膜内进行分离。磷脂酸(PA)和二酰基甘油(DG)都可作为膜脂合成的生物合成前体。它们在时间和空间上是如何被调控的,以及它们通量的变化对有丝分裂保真度有何影响,在很大程度上尚不清楚。利用基因编码的PA和DG探针,我们发现,在裂殖酵母粟酒裂殖酵母有丝分裂期间,DG从内核膜中耗尽,但PA并未积累,这表明它被重新导向膜合成。我们证明,由二酰基甘油激酶Dgk1(也称为Ptp4)催化的DG到PA的转化,以及由二酰基甘油胆碱磷酸转移酶/乙醇胺磷酸转移酶Ept1从DG直接合成甘油磷脂,增强了核膜的扩张。我们得出结论,通过从头合成途径和肯尼迪途径消耗DG,为甘油磷脂生物合成的激增提供了动力,控制着核膜的扩张,并最终控制着有丝分裂保真度。