NEK7 is essential for centriole duplication and centrosomal accumulation of pericentriolar material proteins in interphase cells
NEK7 is essential for centriole duplication and centrosomal accumulation of pericentriolar material proteins in interphase cells
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DOI：
10.1242/jcs.078089
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发表时间：
2011-11-15
影响因子：
4
通讯作者：
Rhee, Kunsoo
中科院分区：
文献类型：
--
作者：
Kim, Sunghwan;Kim, Sungjae;Rhee, Kunsoo
分裂细胞中的中心体遵循一系列重复和分离的周期性事件，这些事件与细胞周期密切相关。丝氨酸/苏氨酸蛋白激酶NEK 7（NEK 7）是一种中心体激酶，在有丝分裂过程中正确的纺锤体形成所需。在这项研究中，我们观察到中心粒复制在NEK 7缺失的细胞中被抑制。异位表达的中心体导向的NEK 7导致额外的中心粒的激酶活性依赖的方式形成。我们还观察到中心体定向NEK 6表达细胞中额外的中心粒形成，表明NEK 6和NEK 7可能具有诱导中心粒复制的生物活性。在NEK 7缺失的细胞中，中心体的中心粒周围物质（PCM）蛋白质显著减少。在NEK 7-耗尽细胞中的PCM蛋白不积累在中心体，即使细胞退出有丝分裂并进展到G2期。这些结果表明，NEK 7是必不可少的PCM积累在细胞周期阶段特异性的方式。此外，HeLa细胞耗尽的NEK 7在S期保留了更高数量的PCM蛋白，并表现出不太严重的有丝分裂表型。基于这些结果，我们提出NEK 7参与了PCM蛋白的募集，这对于中心粒复制和纺锤体极的形成都是必要的。我们的研究表明，NEK 7活性不仅在M期，而且在G1期中心体周期的进展所需的。
The centrosomes in dividing cells follow a series of cyclical events of duplication and separation, which are tightly linked to the cell cycle. Serine/threonine-protein kinase NEK7 (NEK7) is a centrosomal kinase that is required for proper spindle formation during mitosis. In this study, we observed that centriole duplication was inhibited in NEK7-depleted cells. Ectopic expression of centrosomedirected NEK7 led to the formation of extra centrioles in a kinase-activity-dependent manner. We also observed extra centriole formation in centrosome-directed NEK6-expressing cells, suggesting that NEK6 and NEK7 might share biological activities that induce centriole duplication. The centrosomal pericentriolar material (PCM) proteins were significantly reduced in NEK7-depleted cells. The PCM proteins in NEK7-depleted cells did not accumulate at the centrosomes, even if the cells exited mitosis and progressed to the G2 phase. These results revealed that NEK7 is essential for PCM accumulation in a cell cycle stage-specific manner. Furthermore, HeLa cells depleted of NEK7 during S phase retained a higher quantity of PCM proteins and exhibited a less severe mitotic phenotype. On the basis of these results, we propose that NEK7 is involved in the recruitment of PCM proteins, which are necessary for both centriole duplication and spindle pole formation. Our study revealed that NEK7 activity is required for centrosome cycle progression not only at M phase, but also at G1 phase.