Chen Yu-Zen, Zimyanin Vitaly, Redemann Stefanie
Center for Membrane and Cell Physiology, University of Virginia, School of Medicine, Charlottesville, VA, USA.
Department of Molecular Physiology and Biological Physics, University of Virginia, School of Medicine, Charlottesville, VA, USA.
bioRxiv. 2023 Jan 12:2023.01.11.523633. doi: 10.1101/2023.01.11.523633.
In metazoans, Polo Kinase (Plk1) controls several mitotic events including nuclear envelope breakdown, centrosome maturation and kinetochore assembly. Here we show that mitotic events regulated by Polo Like Kinase (PLK-1) in early embryos depend on the mitochondrial-localized protein SPD-3. mutant one-cell embryos contain abnormally positioned mitotic chromosomes and prematurely and asymmetrically disassemble the nuclear lamina. Nuclear envelope breakdown (NEBD) in requires direct dephosphorylation of lamin by PLK-1. In mutants PLK-1 levels are ~6X higher in comparison to control embryos and PLK-1::GFP was highly accumulated at centrosomes, the nuclear envelope, nucleoplasm, and chromosomes prior to NEBD. Partial depletion of in mutant embryos rescued mitotic chromosome and spindle positioning defects indicating that these phenotypes result from higher PLK-1 levels and thus activity. Our data suggests that the mitochondrial SPD-3 protein controls NEBD and chromosome positioning by regulating the endogenous levels of PLK-1 during early embryogenesis in . This finding suggests a novel link between mitochondria and mitotic events by controlling the amount of a key mitotic regulator, PLK-1 and thus may have further implications in the context of cancers or age-related diseases and infertility as it provides a novel link between mitochondria and mitosis.
在多细胞动物中，Polo激酶（Plk1）控制着多个有丝分裂事件，包括核膜破裂、中心体成熟和动粒组装。在此我们表明，早期胚胎中由类Polo激酶（PLK-1）调控的有丝分裂事件依赖于线粒体定位蛋白SPD-3。突变的单细胞胚胎含有位置异常的有丝分裂染色体，并且过早且不对称地拆解核纤层。秀丽隐杆线虫中的核膜破裂（NEBD）需要PLK-1对核纤层蛋白进行直接去磷酸化。在秀丽隐杆线虫突变体中，与对照胚胎相比，PLK-1水平高约6倍，并且在NEBD之前，PLK-1::GFP在中心体、核膜、核质和染色体处高度积累。在秀丽隐杆线虫突变体胚胎中部分耗尽SPD-3可挽救有丝分裂染色体和纺锤体定位缺陷，这表明这些表型是由较高的PLK-1水平及其活性导致的。我们的数据表明，线粒体SPD-3蛋白通过在秀丽隐杆线虫早期胚胎发育过程中调节PLK-1的内源性水平来控制NEBD和染色体定位。这一发现揭示了线粒体与有丝分裂事件之间的一种新联系，即通过控制关键有丝分裂调节因子PLK-1的量来实现，因此可能在癌症、年龄相关疾病和不孕症方面具有进一步的意义，因为它提供了线粒体与有丝分裂之间的新联系。
