Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
J Cell Biol. 2009 Dec 14;187(6):905-20. doi: 10.1083/jcb.200908019.
Centrioles are the foundation for centrosome and cilia formation. The biogenesis of centrioles is initiated by an assembly mechanism that first synthesizes the ninefold symmetrical cartwheel and subsequently leads to a stable cylindrical microtubule scaffold that is capable of withstanding microtubule-based forces generated by centrosomes and cilia. We report that the conserved WD40 repeat domain-containing cartwheel protein Poc1 is required for the structural maintenance of centrioles in Tetrahymena thermophila. Furthermore, human Poc1B is required for primary ciliogenesis, and in zebrafish, DrPoc1B knockdown causes ciliary defects and morphological phenotypes consistent with human ciliopathies. T. thermophila Poc1 exhibits a protein incorporation profile commonly associated with structural centriole components in which the majority of Poc1 is stably incorporated during new centriole assembly. A second dynamic population assembles throughout the cell cycle. Our experiments identify novel roles for Poc1 in centriole stability and ciliogenesis.
中心体是中心粒和纤毛形成的基础。中心粒的生物发生是由一个组装机制启动的,该机制首先合成九倍对称的车轮状结构,随后导致稳定的圆柱形微管支架的形成,该支架能够承受由中心体和纤毛产生的基于微管的力。我们报告说,保守的 WD40 重复结构域包含的车轮状蛋白 Poc1 对于四膜虫热变形虫中心粒的结构维持是必需的。此外,人类 Poc1B 对于初级纤毛发生是必需的,并且在斑马鱼中,DrPoc1B 的敲低导致纤毛缺陷和与人类纤毛病一致的形态表型。T. thermophila Poc1 表现出与结构中心粒成分相关的蛋白掺入谱,其中在新的中心粒组装过程中,大多数 Poc1 稳定地掺入。第二个动态群体在整个细胞周期中组装。我们的实验确定了 Poc1 在中心粒稳定性和纤毛发生中的新作用。