Diacylglycerol at the inner nuclear membrane fuels nuclear envelope expansion in closed mitosis
Diacylglycerol at the inner nuclear membrane fuels nuclear envelope expansion in closed mitosis
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内核膜上的二酰基甘油促进闭合有丝分裂中的核膜扩张
DOI：
10.1101/2022.06.01.494365
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Foo S
中科院分区：
文献类型：
--
作者：
Foo S
必须控制核膜 (NE) 扩张以维持核形状和功能。核膜在闭合有丝分裂过程中大量膨胀，使染色体在完整的 NE 内分离。磷脂酸（PA）和二酰甘油（DG）均可作为膜脂合成的生物合成前体。它们在时间和空间上的调节方式以及它们的通量变化对有丝分裂保真度的影响在很大程度上尚不清楚。使用基因编码的 PA 和 DG 探针，我们发现裂殖酵母裂殖酵母有丝分裂期间 DG 从内核膜耗尽，但 PA 没有积累，表明它被重新路由到膜合成。我们证明，二酰基甘油激酶 Dgk1（也称为 Ptp4）催化的 DG 至 PA 转化以及二酰基甘油磷酸胆碱转移酶/乙醇胺磷酸转移酶 Ept1 从 DG 直接合成甘油磷脂可增强 NE 扩张。我们得出的结论是，通过 de novopathway 和 Kennedy 途径消耗的 DG 促进了甘油磷脂生物合成的激增，控制 NE 扩张，并最终控制有丝分裂保真度。
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 yeastSchizosaccharomyces 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 thede novopathway and the Kennedy pathway fuels a spike in glycerophospholipid biosynthesis, controlling NE expansion and, ultimately, mitotic fidelity.
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