Mofatteh, M. | Search bioRxiv

bioRxiv2021

Centriole distal-end proteins CP110 and Cep97 influence cartwheel growth at the proximal-end of centrioles

Centrioles are composed of a central cartwheel tethered to nine-fold symmetric microtubule (MT) blades. The centriole cartwheel and MTs are thought to grow from opposite ends of these organelles, so it is unclear how they coordinate their assembly. We previously showed that an oscillation of Polo-like kinase 4 (Plk4) helps to initiate and time the growth of the cartwheel at the proximal end. Here, we show that CP110 and Cep97 form a complex close to the distal-end of the centriole MTs whose levels rise and fall as the new centriole MTs grow, entrained by the core Cdk/Cyclin oscillator that drives the nuclear divisions in these embryos. These CP110/Cep97 dynamics, however, do not appear to time the period of centriole MT growth directly. Instead, we find that changing the levels of CP110/Cep97 alters the Plk4 oscillation and the growth of the cartwheel at the proximal end. These findings reveal an unexpected crosstalk between factors normally concentrated at opposite ends of the growing centrioles, which may help to coordinate centriole growth.

cell biology↗

bioRxiv2019

A free-running oscillator times and executes centriole biogenesis

The accurate timing of organelle biogenesis and the precise regulation of organelle size are crucial for cell physiology. Centriole biogenesis initiates exclusively in S-phase, when a daughter centriole emerges from the side of a pre-existing mother and grows until it reaches its mothers size. This process is regulated by Polo-like kinase 4 (Plk4), which is recruited to centrioles in oscillatory waves in flies and human cells 1,2. The nature and function of Plk4 oscillations is, however, unknown. Here we discover that Plk4 forms an adaptive oscillator at the base of the growing centriole, whose function is to time and set the duration of centriole biogenesis in Drosophila embryos. We demonstrate that the Plk4 oscillator is free-running of, but is entrained and calibrated by, the core Cdk/Cyclin cell-cycle oscillator, explaining how centrioles can duplicate independently of the cell cycle 3-5. Mathematical modelling and further experiments indicate that the Plk4 oscillator is generated by a time-delayed negative-feedback loop in which Plk4 recruitment to, and dissociation from, the centriole is monitored via changes in the affinity-state of its centriolar receptor, Asterless. We postulate that such organelle-specific autonomous oscillators could regulate the timing and execution of organelle biogenesis more generally.

cell biology↗