Suppression of Nek2A in mouse early embryos confirms its requirement for chromosome segregation
Suppression of Nek2A in mouse early embryos confirms its requirement for chromosome segregation
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DOI：
10.1242/jcs.01476
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发表时间：
2004-11-01
影响因子：
4
通讯作者：
Rhee, K
中科院分区：
文献类型：
--
作者：
Sonn, S;Khang, I;Rhee, K
Nek2 是曲霉蛋白激酶 NIMA 的哺乳动物结构同源物，主要被认为是控制细胞周期中中心粒-中心粒连接的中心体激酶。然而，其在有丝分裂过程中的动态亚细胞定位表明，除了中心体周期之外，Nek2 可能还参与多种细胞周期事件。为了确定 Nek2 在哺乳动物发育过程中的重要性，我们研究了 Nek2 在小鼠早期胚胎中的表达和功能。我们的结果表明 Nek2A 和 Nek2B 在整个早期胚胎发生过程中均表达。然而，与培养的人类细胞不同，胚胎 Nek2A 在进入有丝分裂时似乎并未被破坏，这表明 Nek2A 蛋白水平在小鼠早期胚胎发生过程中以独特的方式受到控制。 RNAi 抑制 Nek2 表达会导致第二次有丝分裂时的发育缺陷。 Nek2抑制胚胎中的许多卵裂球表现出核形态异常，包括哑铃状核、核桥和微核。这些结果表明 Nek2 对于胚胎有丝分裂中正确的染色体分离的重要性。
Nek2, a mammalian structural homologue of Aspergillus protein kinase NIMA, is predominantly known as a centrosomal kinase that controls centriole-centriole linkage during the cell cycle. However, its dynamic subcellular localization during mitosis suggested that Nek2 might be involved in diverse cell cycle events in addition to the centrosomal cycle. In order to determine the importance of Nek2 during mammalian development, we investigated the expression and function of Nek2 in mouse early embryos. Our results show that both Nek2A and Nek2B were expressed throughout early embryogenesis. Unlike cultured human cells, however, embryonic Nek2A appeared not to be destroyed upon entry into mitosis, suggesting that the Nek2A protein level is controlled in a unique manner during mouse early embryogenesis. Suppression of Nek2 expression by RNAi resulted in developmental defects at the second mitosis. Many of the blastomeres in Nek2-suppressed embryos showed abnormality in nuclear morphology, including dumbbell-like nuclei, nuclear bridges and micronuclei. These results indicate the importance of Nek2 for proper chromosome segregation in embryonic mitoses.