An Autonomous Oscillation Times and Executes Centriole Biogenesis

• Published in: Cell Vol. 181; no. 7; pp. 1566 - 1581.e27
• Main Authors: Aydogan, Mustafa G., Steinacker, Thomas L., Mofatteh, Mohammad, Wilmott, Zachary M., Zhou, Felix Y., Gartenmann, Lisa, Wainman, Alan, Saurya, Saroj, Novak, Zsofia A., Wong, Siu-Shing, Goriely, Alain, Boemo, Michael A., Raff, Jordan W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25-06-2020; Cell Press
• Subjects: Animals; Biological Clocks - physiology; biological oscillator; biological timing; cell cycle; Cell Cycle - physiology; Cell Cycle Proteins - metabolism; centriole; centriole duplication; Centrioles - metabolism; centrosome; Centrosome - metabolism; Drosophila melanogaster - metabolism; Drosophila Proteins - metabolism; Drosophila Proteins - physiology; FCS; Organelle Biogenesis; organelle sizing; Phosphorylation; Protein Serine-Threonine Kinases - metabolism; Protein Serine-Threonine Kinases - physiology; organelle sizing; centriole duplication; biological timing; cell cycle; FCS; organelle biogenesis; biological oscillator; centriole; centrosome
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2020.05.018

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.
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•Centriolar Plk4 levels oscillate and act as a switch for centriole biogenesis•Oscillations may be generated via an Asl/Plk4 delayed negative feedback loop•Plk4 oscillations are entrained and phase-locked by the Cdk/Cyclin oscillator (CCO)•Plk4 oscillations can drive centriole biogenesis even when the CCO is perturbed
Feedback-driven oscillations in centriolar Plk4 kinase levels—normally entrained by the cell-cycle oscillator but capable of running autonomously—trigger and time centriole biogenesis to ensure that daughter centrioles grow at the right time and to the right size.