Abstract
Primary cilia are displayed during the G0/G1 phase of many cell types. Cilia are resorbed as cells prepare to re-enter the cell cycle, but the causal and molecular link between these two cellular events remains unclear. We show that Tctex-1 phosphorylated at Thr 94 is recruited to ciliary transition zones before S-phase entry and has a pivotal role in both ciliary disassembly and cell cycle progression. However, the role of Tctex-1 in S-phase entry is dispensable in non-ciliated cells. Exogenously adding a phospho-mimic Tctex-1T94E mutant accelerates cilium disassembly and S-phase entry. These results support a model in which the cilia act as a brake to prevent cell cycle progression. Mechanistic studies show the involvement of actin dynamics in Tctex-1-regulated cilium resorption. Tctex-1 phosphorylated at Thr 94 is also selectively enriched at the ciliary transition zones of cortical neural progenitors, and has a key role in controlling G1 length, cell cycle entry and fate determination of these cells during corticogenesis.
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Acknowledgements
We are indebted to the following grant support: Tri-Institutional Starr Foundation, NYSTEM, NIH (EY11307, EY016805), RPB (to C-H.S.), Tohoku University (to M.S.), New Energy and Industrial Technology Development Organization, and Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (to K.T.). We thank G. Pazour, K. Anderson, R. Hevner, Y. Shi, N. Heintz, C. Cepko, A. Liu and S. Doxsey for reagents, and S. Anderson, M. E. Ross, D. Cobrinik and B. Tsou for discussion.
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A.L., J-Z.C. and C-H.S designed the overall study. A.L. and C.D. performed IUE experiments and phenotype characterization. J-Z. C. generated all constructs. A. L., Y-Y.T. and M.S. performed cell culture studies. K.T. generated the anti-phospho(T94)Tctex-1 antibody. K.T. and T.K. generated 9R peptides. A.L., J-Z.C. and C-H.S. wrote the paper.
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Li, A., Saito, M., Chuang, JZ. et al. Ciliary transition zone activation of phosphorylated Tctex-1 controls ciliary resorption, S-phase entry and fate of neural progenitors. Nat Cell Biol 13, 402–411 (2011). https://doi.org/10.1038/ncb2218
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DOI: https://doi.org/10.1038/ncb2218
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