Calibrated mitotic oscillator drives motile ciliogenesis
Calibrated mitotic oscillator drives motile ciliogenesis
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DOI：
10.1126/science.aan8311
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发表时间：
2017-11-10
期刊：
影响因子：
56.9
通讯作者：
Meunier, Alice
中科院分区：
文献类型：
--
作者：
Al Jord, Adel;Shihavuddin, Asm;Meunier, Alice
细胞分裂和分化依赖于大量和快速的细胞器重塑。有丝分裂振荡器，集中在细胞周期蛋白依赖性激酶1-后期促进复合物/细胞周期体（CDK 1-APC/C）轴，时空协调分裂细胞的重组。在这里，我们发现，非分裂细胞也可以执行这种有丝分裂时钟样调节回路，以协调与分化相关的亚细胞重组。我们探讨了分化小鼠脑多纤毛细胞的中心粒扩增。这些有丝分裂后的祖细胞微调有丝分裂振荡器的活动，以驱动有序的进程，中心粒的生产，成熟和运动纤毛，同时避免有丝分裂承诺阈值。CDK 1活性不足阻碍分化，而过度的活性加速分化，但驱动有丝分裂后的祖细胞进入有丝分裂。因此，有丝分裂后的细胞可以重新部署和校准有丝分裂振荡器，以解偶联细胞质从核动力学与分化相关的细胞器重塑。
Cell division and differentiation depend on massive and rapid organelle remodeling. The mitotic oscillator, centered on the cyclin-dependent kinase 1-anaphase-promoting complex/cyclosome (CDK1-APC/C) axis, spatiotemporally coordinates this reorganization in dividing cells. Here we discovered that nondividing cells could also implement this mitotic clocklike regulatory circuit to orchestrate subcellular reorganization associated with differentiation. We probed centriole amplification in differentiating mouse-brain multiciliated cells. These postmitotic progenitors fine-tuned mitotic oscillator activity to drive the orderly progression of centriole production, maturation, and motile ciliation while avoiding the mitosis commitment threshold. Insufficient CDK1 activity hindered differentiation, whereas excessive activity accelerated differentiation yet drove postmitotic progenitors into mitosis. Thus, postmitotic cells can redeploy and calibrate the mitotic oscillator to uncouple cytoplasmic from nuclear dynamics for organelle remodeling associated with differentiation.