Centriole distal appendages promote membrane docking, leading to cilia initiation

被引:300
作者
Tanos, Barbara E. [1 ]
Yang, Hui-Ju [1 ]
Soni, Rajesh [1 ]
Wang, Won-Jing [1 ]
Macaluso, Frank P. [2 ]
Asara, John M. [3 ,4 ]
Tsou, Meng-Fu Bryan [1 ,5 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10065 USA
[2] Albert Einstein Coll Med, Analyt Imaging Facil, Bronx, NY 10461 USA
[3] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[4] Beth Israel Deaconess Med Ctr, Mass Spectrometry Core, Boston, MA 02115 USA
[5] Cornell Univ, Weill Cornell Grad Sch Med Sci, New York, NY 10065 USA
基金
美国国家卫生研究院;
关键词
centriole; cilia; distal appendages; transition fibers; membrane docking; CELL-CYCLE; DUPLICATION; PROTEOMICS; TRANSPORT; BARRIER; BASE;
D O I
10.1101/gad.207043.112
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:163 / 168
页数:6
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