Centriole distal appendages promote membrane docking, leading to cilia initiation
Centriole distal appendages promote membrane docking, leading to cilia initiation
复制标题
DOI：
10.1101/gad.207043.112
复制
发表时间：
2013-01-15
影响因子：
10.5
通讯作者：
Tsou, Meng-Fu Bryan
中科院分区：
文献类型：
--
作者：
Tanos, Barbara E.;Yang, Hui-Ju;Tsou, Meng-Fu Bryan
中心粒的远端附属物（DAP）已被提议将纤毛固定在质膜上，但它们的分子组成、组装和纤毛发生中的确切功能仍然知之甚少。使用定量中心体蛋白质组学和超分辨率显微镜，我们鉴定了五种 DAP 成分，包括一种先前描述的 (CEP164)、一种部分表征的 (CEP89 [ccdc123]) 和三种新型 (CEP83 [ccdc41]、SCLT1 和 FBF1) DAP 蛋白。对 DAP 组装的分析揭示了一个层次结构。 CEP83 将 SCLT1 和 CEP89 招募到中心粒。随后 FBF1 和 CEP164 的募集独立于 CEP89，但由 SCLT1 介导。所有五种 DAP 成分对于纤毛发生都是必需的； CEP83 的缺失会特异性地阻碍中心粒与膜的对接。未对接的中心粒无法招募 TTBK2 或释放 CP110，这是在纤毛组装之前在中心粒上发现的两个最早的修饰，揭示了中心粒与膜的对接是促进纤毛起始的时间和空间线索。
The distal appendages (DAPs) of centrioles have been proposed to anchor cilia to the plasma membrane, but their molecular composition, assembly, and exact function in ciliogenesis remain poorly understood. Using quantitative centrosome proteomics and superresolution microscopy, we identified five DAP components, including one previously described (CEP164), one partially characterized (CEP89 [ccdc123]), and three novel (CEP83 [ccdc41], SCLT1, and FBF1) DAP proteins. Analyses of DAP assembly revealed a hierarchy. CEP83 recruits both SCLT1 and CEP89 to centrioles. Subsequent recruitment of FBF1 and CEP164 is independent of CEP89 but mediated by SCLT1. All five DAP components are essential for ciliogenesis; loss of CEP83 specifically blocks centriole-to-membrane docking. Undocked centrioles fail to recruit TTBK2 or release CP110, the two earliest modifications found on centrioles prior to cilia assembly, revealing centriole-to-membrane docking as a temporal and spatial cue promoting cilia initiation.