Temporal Regulation of Lipin Activity Diverged to Account for Differences in Mitotic Programs.
Temporal Regulation of Lipin Activity Diverged to Account for Differences in Mitotic Programs.
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DOI：
10.1016/j.cub.2015.11.061
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发表时间：
2016-01-25
期刊：
影响因子：
--
通讯作者：
Oliferenko S
中科院分区：
文献类型：
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作者：
Makarova M;Gu Y;Chen JS;Beckley JR;Gould KL;Oliferenko S
真核生物在有丝分裂过程中使用不同的机制来重塑细胞核，这些机制在核膜破裂的时间和程度上有所不同。在这里，我们通过利用相关分裂酵母菌裂殖酵母和日本裂殖酵母在NE管理策略上的自然差异来探索使这种功能多样性的原理。我们表明，通过CDK磷酸化使Lipin家族的磷脂酸磷酸酶Ned1失活是必要的，也是充分的，以促进金黄色葡萄球菌“闭合”有丝分裂所需的NE扩张。相比之下，Ned1在日本血吸虫的分裂过程中不受调控，因此限制了膜的可获得性，并需要NE断裂。种间基因交换导致表型正常的分裂，日本血吸虫脂肪获得了血吸虫样有丝分裂磷酸化模式。我们的结果为磷脂酸通量的有丝分裂调节提供了实验证据，并表明控制脂类活性的调节网络在进化过程中出现了分歧，导致了截然不同的有丝分裂程序。在封闭的有丝分裂中，依赖CDK的脂类磷酸化是关闭有丝分裂所必需的。在近缘物种中，脂类不受有丝分裂CDK的调节。揭示有丝分裂过程中核膜扩张的可变性的分子基础。他们表明，经历封闭有丝分裂的细胞在分裂前通过携带磷脂流动调节剂脂类的失活来扩大其核膜，以获得高CDK活性。
Eukaryotes remodel the nucleus during mitosis using a variety of mechanisms that differ in the timing and the extent of nuclear envelope (NE) breakdown. Here, we probe the principles enabling this functional diversity by exploiting the natural divergence in NE management strategies between the related fission yeasts Schizosaccharomyces pombe and Schizosaccharomyces japonicus. We show that inactivation of Ned1, the phosphatidic acid phosphatase of the lipin family, by CDK phosphorylation is both necessary and sufficient to promote NE expansion required for “closed” mitosis in S. pombe. In contrast, Ned1 is not regulated during division in S. japonicus, thus limiting membrane availability and necessitating NE breakage. Interspecies gene swaps result in phenotypically normal divisions with the S. japonicus lipin acquiring an S. pombe-like mitotic phosphorylation pattern. Our results provide experimental evidence for the mitotic regulation of phosphatidic acid flux and suggest that the regulatory networks governing lipin activity diverged in evolution to give rise to strikingly dissimilar mitotic programs. Lipin phosphorylation by CDK drives mitotic nuclear envelope expansion in S. pombe CDK-dependent lipin phosphorylation is required for closed mitosis Lipin is not regulated by mitotic CDK in the related species S. japonicus Interspecies gene swaps reveal species-specific trans-regulation of lipin activity Using closely related yeasts, Makarova et al. uncover a molecular basis for variability in nuclear envelope expansion during mitosis. They show that cells undergoing closed mitosis expand their nuclear envelope prior to division by entraining inactivation of the phosphatidic acid flux regulator lipin to high CDK activity.