Ciliary transition zone activation of phosphorylated Tctex-1 controls ciliary resorption, S-phase en

Abstract

Ciliogenesis starts as cells enter quiescence and primary cilium resorption precedes mitosis. Phosphorylation of Tctex1 is found to accelerate cilium disassembly and S-phase entry in ciliated cells, providing a molecular link between ciliogenesis and the cell cycle. Phospho-Tctex1 action requires an intact actin cytoskeleton and may be relevant for fate determination of cortical neural progenitors. 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.

Cite this article

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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