Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Nat Cell Biol. 2011 Apr;13(4):402-11. doi: 10.1038/ncb2218. Epub 2011 Mar 13.
Primary cilia are displayed during the G(0)/G(1) 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-1(T94E) 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 G(1) length, cell cycle entry and fate determination of these cells during corticogenesis.
初级纤毛在许多细胞类型的 G(0)/G(1) 期都有显示。纤毛在细胞准备重新进入细胞周期时被吸收，但这两个细胞事件之间的因果和分子联系尚不清楚。我们表明，Tctex-1 在 Thr 94 处被磷酸化，在进入 S 期之前被募集到纤毛过渡区，并在纤毛解体和细胞周期进程中都起着关键作用。然而，在非纤毛细胞中，Tctex-1 在 S 期进入中的作用是可有可无的。外源性添加磷酸模拟 Tctex-1(T94E)突变体加速了纤毛解体和 S 期进入。这些结果支持了一种模型，即纤毛作为一种制动器，阻止细胞周期的进展。机制研究表明，肌动蛋白动力学参与了 Tctex-1 调节的纤毛吸收。在皮质神经祖细胞的纤毛过渡区，磷酸化的 Tctex-1 在 Thr 94 处也被选择性富集，并在控制这些细胞的 G(1)长度、细胞周期进入和命运决定方面发挥关键作用。
