Cell Cycle Control and Carcinogenesis, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
J Cell Sci. 2012 Jan 15;125(Pt 2):486-96. doi: 10.1242/jcs.093930. Epub 2012 Feb 2.
Centriole duplication occurs once per cell cycle and requires Plk4, a member of the Polo-like kinase family. A key component of the centrosome is the γ-tubulin ring complex (γ-TuRC) that nucleates microtubules. GCP6 is a member of the γ-TuRC, but its role in human cells and the regulation of its functions remain unclear. Here we report that depletion of human GCP6 prevents assembly of the γ-TuRC and induces a high percentage of monopolar spindles. These spindles are characterized by a loss of centrosomal γ-tubulin and reduced centriole numbers. We found that GCP6 is localized in the pericentriolar material but also at distal portions of centrioles. In addition, GCP6 is required for centriole duplication and Plk4-induced centriole overduplication. GCP6 interacts with and is phosphorylated by Plk4. Moreover, we find that Plk4-dependent phosphorylation of GCP6 regulates centriole duplication. These data suggest that GCP6 is a target of Plk4 in centriole biogenesis.
中心体复制发生在每个细胞周期一次,需要 Polo 样激酶家族的成员 Plk4。中心体的一个关键组成部分是γ-微管蛋白环复合物(γ-TuRC),它能起始微管的形成。GCP6 是γ-TuRC 的一个成员,但它在人类细胞中的作用及其功能的调节仍不清楚。在这里,我们报告说,人源 GCP6 的缺失会阻止 γ-TuRC 的组装,并诱导出高比例的单极纺锤体。这些纺锤体的特征是中心体 γ-微管蛋白的丢失和中心体数量的减少。我们发现 GCP6 定位于中心粒周围物质中,但也存在于中心粒的远端部分。此外,GCP6 是中心体复制和 Plk4 诱导的中心体过度复制所必需的。GCP6 与 Plk4 相互作用并被 Plk4 磷酸化。此外,我们发现 Plk4 依赖性磷酸化 GCP6 调节中心体复制。这些数据表明,GCP6 是中心体生物发生中 Plk4 的一个靶标。