Brieño-Enríquez Miguel A, Moak Stefannie L, Holloway J Kim, Cohen Paula E
Department of Biomedical Sciences and Center for Reproductive Genomics, Cornell University, Ithaca, New York, United States of America.
PLoS One. 2017 Oct 5;12(10):e0185780. doi: 10.1371/journal.pone.0185780. eCollection 2017.
NIMA-related kinase 1 (NEK1) is a serine/threonine and tyrosine kinase that is highly expressed in mammalian germ cells. Mutations in Nek1 induce anemia, polycystic kidney and infertility. In this study we evaluated the role of NEK1 in meiotic spindle formation in both male and female gametes. Our results show that the lack of NEK1 provokes an abnormal organization of the meiosis I spindle characterized by elongated and/or multipolar spindles, and abnormal chromosome congression. The aberrant spindle structure is concomitant with the disruption in localization and protein levels of myosin X (MYO10) and α-adducin (ADD1), both of which are implicated in the regulation of spindle formation during mitosis. Interaction of ADD1 with MYO10 is dependent on phosphorylation, whereby phosphorylation of ADD1 enables its binding to MYO10 on mitotic spindles. Reduction in ADD1 protein in NEK1 mutant mice is associated with hyperphosphorylation of ADD1, thereby preventing the interaction with MYO10 during meiotic spindle formation. Our results reveal a novel regulatory role for NEK1 in the regulation of spindle architecture and function during meiosis.
NIMA相关激酶1(NEK1)是一种丝氨酸/苏氨酸和酪氨酸激酶,在哺乳动物生殖细胞中高度表达。Nek1突变会导致贫血、多囊肾和不育。在本研究中,我们评估了NEK1在雄性和雌性配子减数分裂纺锤体形成中的作用。我们的结果表明,NEK1的缺失会引发减数分裂I纺锤体的异常组织,其特征为纺锤体拉长和/或多极,以及染色体排列异常。异常的纺锤体结构与肌球蛋白X(MYO10)和α-内收蛋白(ADD1)的定位和蛋白质水平的破坏同时出现,这两者都与有丝分裂期间纺锤体形成的调节有关。ADD1与MYO10的相互作用依赖于磷酸化,由此ADD1的磷酸化使其能够在有丝分裂纺锤体上与MYO10结合。NEK1突变小鼠中ADD1蛋白的减少与ADD1的过度磷酸化有关,从而在减数分裂纺锤体形成过程中阻止其与MYO10的相互作用。我们的结果揭示了NEK1在减数分裂期间纺锤体结构和功能调节中的一种新的调节作用。