The accurate timing and execution of organelle biogenesis is crucial for cell physiology. Centriole biogenesis is regulated by Polo-like kinase 4 (Plk4) and initiates in S-phase when a daughter centriole grows from the side of a pre-existing mother. Here, we show that a Plk4 oscillation at the base of the growing centriole initiates and times centriole biogenesis to ensure that centrioles grow at the right time and to the right size. The Plk4 oscillation is normally entrained to the cell-cycle oscillator but can run autonomously of it—potentially explaining why centrioles can duplicate independently of cell-cycle progression. Mathematical modeling indicates that the Plk4 oscillation can be generated by a time-delayed negative feedback loop in which Plk4 inactivates the interaction with its centriolar receptor through multiple rounds of phosphorylation. We hypothesize that similar organelle-specific oscillations could regulate the timing and execution of organelle biogenesis more generally.

细胞器生物发生的准确时间和执行对于细胞生理学至关重要。中心粒生物发生由 Polo 样激酶 4 (Plk4) 调节，并在子中心粒从先前存在的母亲一侧生长时在 S 期开始。在这里，我们展示了在生长中心粒底部的 Plk4 振荡启动并计时中心粒生物发生，以确保中心粒在正确的时间和正确的大小生长。Plk4 振荡通常被带入细胞周期振荡器，但可以自主运行——这可能解释了为什么中心粒可以独立于细胞周期进程进行复制。数学模型表明，Plk4 振荡可以由延时负反馈回路产生，其中 Plk4 通过多轮磷酸化使其与其中心受体的相互作用失活。我们假设类似的细胞器特异性振荡可以更普遍地调节细胞器生物发生的时间和执行。