CEP55 promotes cilia disassembly through stabilizing Aurora A kinase

• Published in: The Journal of cell biology Vol. 220; no. 2
• Main Authors: Zhang, Yu-Cheng, Bai, Yun-Feng, Yuan, Jin-Feng, Shen, Xiao-Lin, Xu, Yu-Ling, Jian, Xiao-Xiao, Li, Sen, Song, Zeng-Qing, Hu, Huai-Bin, Li, Pei-Yao, Tu, Hai-Qing, Han, Qiu-Ying, Wang, Na, Li, Ai-Ling, Zhang, Xue-Min, Wu, Min, Zhou, Tao, Li, Hui-Yan
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 01.02.2021
• Subjects: Abnormalities; Animals; Aurora Kinase A - metabolism; Cell Cycle Checkpoints; Cell Cycle Proteins - deficiency; Cell Cycle Proteins - metabolism; Cell surface; Cells, Cultured; Centrosome - metabolism; Centrosome - ultrastructure; Chaperonin Containing TCP-1 - metabolism; Cilia; Cilia - metabolism; Cilia - ultrastructure; Ciliary Motility Disorders - pathology; Defects; Development; Disease; Dismantling; Elongation; Encephalocele - pathology; Enzyme Stability; Gene Targeting; HEK293 Cells; Humans; In vivo methods and tests; Inactivation; Kidneys; Kinases; Mice; Mitosis; Mutation; Phenotype; Polycystic kidney; Polycystic Kidney Diseases - pathology; Protein Binding; Retinitis Pigmentosa - pathology; Smoothened Receptor - metabolism
• ISSN: 0021-9525; 1540-8140; 1540-8140
• DOI: 10.1083/jcb.202003149

Primary cilia protrude from the cell surface and have diverse roles during development and disease, which depends on the precise timing and control of cilia assembly and disassembly. Inactivation of assembly often causes cilia defects and underlies ciliopathy, while diseases caused by dysfunction in disassembly remain largely unknown. Here, we demonstrate that CEP55 functions as a cilia disassembly regulator to participate in ciliopathy. Cep55−/− mice display clinical manifestations of Meckel–Gruber syndrome, including perinatal death, polycystic kidneys, and abnormalities in the CNS. Interestingly, Cep55−/− mice exhibit an abnormal elongation of cilia on these tissues. Mechanistically, CEP55 promotes cilia disassembly by interacting with and stabilizing Aurora A kinase, which is achieved through facilitating the chaperonin CCT complex to Aurora A. In addition, CEP55 mutation in Meckel–Gruber syndrome causes the failure of cilia disassembly. Thus, our study establishes a cilia disassembly role for CEP55 in vivo, coupling defects in cilia disassembly to ciliopathy and further suggesting that proper cilia dynamics are critical for mammalian development.