Mitotic events depend on regulation of PLK-1 levels by the mitochondrial protein SPD-3.
Mitotic events depend on regulation of PLK-1 levels by the mitochondrial protein SPD-3.
复制标题
有丝分裂事件取决于线粒体蛋白 SPD-3 对 PLK-1 水平的调节。
DOI：
10.1101/2023.01.11.523633
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Redemann,Stefanie
中科院分区：
文献类型：
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作者：
Chen,Yu-Zen;Zimyanin,Vitaly;Redemann,Stefanie
在后生动物中，波罗激酶（Plk 1）控制几个有丝分裂事件，包括核膜破裂、中心体成熟和动粒组装。在此，我们发现在C.线虫的胚胎依赖于细胞定位的蛋白SPD-3。SPD-3突变单细胞胚胎含有异常定位的有丝分裂染色体，并且过早地和不对称地分解核纤层。核膜破裂（NEBD）。elegans需要PLK-1直接使核纤层蛋白去磷酸化。在spd-3突变体中，PLK-1水平比对照胚胎高约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。spd-3突变体胚胎中plk-1的部分缺失挽救了有丝分裂染色体和纺锤体定位缺陷，表明这些表型是由更高的PLK-1水平和活性引起的。我们的数据表明，线粒体SPD-3蛋白控制NEBD和染色体定位通过调节内源性PLK-1水平在早期胚胎发生在C。优雅的这一发现表明，通过控制关键的有丝分裂调节因子PLK-1的量，线粒体和有丝分裂事件之间存在新的联系，因此可能在癌症或年龄相关疾病和不育症的背景下具有进一步的意义，因为它提供了线粒体和有丝分裂之间的新联系。
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 C. elegans embryos depend on the mitochondrial-localized protein SPD-3. spd-3 mutant one-cell embryos contain abnormally positioned mitotic chromosomes and prematurely and asymmetrically disassemble the nuclear lamina. Nuclear envelope breakdown (NEBD) in C. elegans requires direct dephosphorylation of lamin by PLK-1. In spd-3 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 plk-1 in spd-3 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 C. elegans. 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.