State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Nat Cell Biol. 2013 Dec;15(12):1434-44. doi: 10.1038/ncb2880. Epub 2013 Nov 17.
Dense multicilia in higher vertebrates are important for luminal flow and the removal of thick mucus. To generate hundreds of basal bodies for multiciliogenesis, specialized terminally differentiated epithelial cells undergo massive centriole amplification. In proliferating cells, however, centriole duplication occurs only once per cell cycle. How cells ensure proper regulation of centriole biogenesis in different contexts is poorly understood. We report that the centriole amplification is controlled by two duplicated genes, Cep63 and Deup1. Cep63 regulates mother-centriole-dependent centriole duplication. Deup1 governs deuterosome assembly to mediate large-scale de novo centriole biogenesis. Similarly to Cep63, Deup1 binds to Cep152 and then recruits Plk4 to activate centriole biogenesis. Phylogenetic analyses suggest that Deup1 diverged from Cep63 in a certain ancestor of lobe-finned fishes during vertebrate evolution and was subsequently adopted by tetrapods. Thus, the Cep63 gene duplication has enabled mother-centriole-independent assembly of the centriole duplication machinery to satisfy different requirements for centriole number.
高等脊椎动物的密集多纤毛对于管腔流动和厚黏液的清除很重要。为了产生数百个用于多纤毛发生的基体，专门的终末分化上皮细胞经历大量中心体扩增。然而，在增殖细胞中，中心体复制每个细胞周期仅发生一次。细胞如何确保在不同情况下正确调节中心体发生仍知之甚少。我们报告称，中心体扩增受两个复制基因 Cep63 和 Deup1 控制。Cep63 调节母中心体依赖性中心体复制。Deup1 控制后致密体组装以介导大规模新中心体发生。与 Cep63 类似，Deup1 结合 Cep152 然后招募 Plk4 激活中心体发生。系统发育分析表明，在脊椎动物进化过程中，Deup1 从 Cep63 在某些肉鳍鱼类的祖先中分化出来，随后被四足动物采用。因此，Cep63 基因复制使母中心体独立的中心体复制机制的组装能够满足中心体数量的不同要求。
