Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.
Genes (Basel). 2011 Mar 7;2(1):260-79. doi: 10.3390/genes2010260.
Meiosis is a highly conserved process, which is stringently regulated in all organisms, from fungi through to humans. Two major events define meiosis in eukaryotes. The first is the pairing, or synapsis, of homologous chromosomes and the second is the exchange of genetic information in a process called meiotic recombination. Synapsis is mediated by the meiosis-specific synaptonemal complex structure in combination with the cohesins that tether sister chromatids together along chromosome arms through prophase I. Previously, we identified FKBP6 as a novel component of the mammalian synaptonemal complex. Further studies demonstrated an interaction between FKBP6 and the NIMA-related kinase-1, NEK1. To further investigate the role of NEK1 in mammalian meiosis, we have examined gametogenesis in the spontaneous mutant, Nek1kat2J. Homozygous mutant animals show decreased testis size, defects in testis morphology, and in cohesin removal at late prophase I of meiosis, causing complete male infertility. Cohesin protein SMC3 remains localized to the meiotic chromosome cores at diplonema in the Nek1 mutant, and also in the related Fkbp6 mutant, while in wild type cells SMC3 is removed from the cores at the end of prophase I and becomes more diffuse throughout the DAPI stained region of the nucleus. These data implicate NEK1 as a possible kinase involved in cohesin redistribution in murine spermatocytes.
减数分裂是一个高度保守的过程，在从真菌到人类的所有生物中都受到严格的调控。两个主要事件定义了真核生物的减数分裂。第一个是同源染色体的配对或联会，第二个是在称为减数分裂重组的过程中交换遗传信息。联会是由减数分裂特异性联会复合体结构与黏着蛋白共同介导的，黏着蛋白通过前期 I 将姐妹染色单体沿着染色体臂系在一起。此前，我们鉴定 FKBP6 为哺乳动物联会复合体的一个新成分。进一步的研究表明 FKBP6 与 NIMA 相关激酶-1（NEK1）之间存在相互作用。为了进一步研究 NEK1 在哺乳动物减数分裂中的作用，我们检查了自发性突变体 Nek1kat2J 的配子发生情况。纯合突变体动物的睾丸体积减小，睾丸形态缺陷，减数分裂前期 I 晚期的黏着蛋白去除缺陷，导致完全雄性不育。在 Nek1 突变体中，黏合蛋白 SMC3 仍定位于减数分裂染色体核心的二联体期，在相关的 Fkbp6 突变体中也是如此，而在野生型细胞中，SMC3 在前期 I 结束时从核心中去除，并在细胞核的 DAPI 染色区域变得更加弥散。这些数据表明 NEK1 可能是一种参与小鼠精母细胞黏合蛋白重分布的激酶。
