https://scholars.lib.ntu.edu.tw/handle/123456789/559268
標題: | Phosphorylation of CEP83 by TTBK2 is necessary for cilia initiation | 作者: | Lo, C.-H. Lin, I.-H. Yang, T.T. Huang, Y.-C. Tanos, B.E. Chou, P.-C. Chang, C.-W. Tsay, Y.-G. Liao, J.-C. Wang, W.-J. TUNG-LIN YANG |
公開日期: | 2019 | 卷: | 218 | 期: | 10 | 起(迄)頁: | 3489-3505 | 來源出版物: | Journal of Cell Biology | 摘要: | Primary cilia are microtubule-based organelles that play important roles in development and tissue homeostasis. Tau-tubulin kinase-2 (TTBK2) is genetically linked to spinocerebellar ataxia type 11, and its kinase activity is crucial for ciliogenesis. Although it has been shown that TTBK2 is recruited to the centriole by distal appendage protein CEP164, little is known about TTBK2 substrates associated with its role in ciliogenesis. Here, we perform superresolution microscopy and discover that serum starvation results in TTBK2 redistribution from the periphery toward the root of distal appendages. Our biochemical analyses uncover CEP83 as a bona fide TTBK2 substrate with four phosphorylation sites characterized. We also demonstrate that CEP164-dependent TTBK2 recruitment to distal appendages is required for subsequent CEP83 phosphorylation. Specifically, TTBK2-dependent CEP83 phosphorylation is important for early ciliogenesis steps, including ciliary vesicle docking and CP110 removal. In summary, our results reveal a molecular mechanism of kinase regulation in ciliogenesis and identify CEP83 as a key substrate of TTBK2 during cilia initiation. © 2019 Lo et al. |
URI: | https://www.scopus.com/inward/record.url?eid=2-s2.0-85072993722&partnerID=40&md5=ecb37e6b2ebc1042a664e461298dffe1 https://scholars.lib.ntu.edu.tw/handle/123456789/559268 |
ISSN: | 00219525 | DOI: | 10.1083/JCB.201811142 | SDG/關鍵字: | phosphotransferase; protein CEP83; Tau tubulin kinase 2; unclassified drug; CEP83 protein, human; microtubule associated protein; protein serine threonine kinase; tau-tubulin kinase; Article; biochemical analysis; cell growth; cell vacuole; centriole; cilium; controlled study; enzyme activity; enzyme analysis; enzyme phosphorylation; enzyme regulation; enzyme substrate; human; human cell; molecular docking; priority journal; cell culture; cilium; HEK293 cell line; metabolism; phosphorylation; Cells, Cultured; Cilia; HEK293 Cells; Humans; Microtubule-Associated Proteins; Phosphorylation; Protein-Serine-Threonine Kinases |
顯示於: | 電機工程學系 |
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