An Autonomous Oscillation Times and Executes Centriole Biogenesis

Mustafa G Aydogan,Thomas L Steinacker,Mohammad Mofatteh,Zachary M Wilmott,Felix Y Zhou,Lisa Gartenmann,Alan Wainman,Saroj Saurya,Zsofia A Novak,Siu-Shing Wong,Alain Goriely,Michael A Boemo,Jordan W Raff

doi:10.1016/j.cell.2020.05.018

Abstract

SummaryThe 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.

Highlights

Albert Claude’s landmark paper (Claude, 1943) challenged the idea that cells are a mere bag of enzymes whose contents grow freely in the cytoplasm with no active regulation
Centriolar Polo-like kinase 4 (Plk4)-NG levels oscillated during each cycle: levels started to rise in M-phase, peaked in earlymid S-phase, and were minimal by the M-phase (Figures 1A and S2A)
The Plk4 oscillations appeared to be entrained by the core Cdk/Cyclin oscillator as their period increased as nuclear cycles slowed during cycles 11–13 (Figure 1C)

Summary

Introduction

Albert Claude’s landmark paper (Claude, 1943) challenged the idea that cells are a mere bag of enzymes whose contents grow freely in the cytoplasm with no active regulation. Centrioles are highly structured organelles that form centrosomes and cilia (Bettencourt-Dias et al, 2011; Nigg and Holland, 2018; Nigg and Raff, 2009) Their linear structure and tightly controlled pattern of duplication makes them an attractive model with which to study organelle biogenesis (Goehring and Hyman, 2012; Marshall, 2016). To monitor the dynamics of centriole growth, we recently examined living syncytial Drosophila embryos where we could follow the assembly of hundreds of centrioles as they duplicate in near-synchrony in a common cytoplasm (Aydogan et al, 2018).

Methods

Results

Conclusion