Evidence that sub-cellular oscillators may time and execute organelle biogenesis

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• Jordan Raff
• Thursday 20 September 2018, 16:00-17:00
• Max Perutz Lecture Theatre, Medical Research Council (MRC) (MRC Laboratory of Molecular Biol.

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The accurate timing and execution of organelle biogenesis is crucial for cell physiology, yet we have little idea about how these processes are regulated. In order to study this question, we recently established the Drosophila centriole as a model, as its linear structure makes its biogenesis easy to define and measure. Centriole biogenesis occurs only in S-phase and it is strictly regulated by Polo-like kinase 4 (Plk4). Unexpectedly, we find that centriole growth in early Drosophila embryos is homeostatic: When centrioles grow slowly, they grow for a longer period; when centrioles grow quickly, they grow for a shorter period. This ensures that centrioles grow to a consistent size. Plk4 is localized at the base of the growing daughter centriole and it sets both the rate and period of daughter centriole growth. The activity of Plk4 kinase controls the growth rate, but how Plk4 determines the growth period is unclear. I will discuss our recent data that suggests that Plk4 forms an adaptive oscillator at the base of the growing centriole, whose propagation times and sets the duration of centriole biogenesis in Drosophila embryos. The Plk4 oscillator appears to be free-running of, but entrained and calibrated by, the core Cdk/Cyclin cell-cycle oscillator. Mathematical modelling and experimental evidence indicate that Plk4 oscillations are generated by a time-delayed negative-feedback loop. We speculate that such free-running oscillators could regulate the timing and execution of organelle biogenesis more generally.

This talk is part of the MRC LMB Seminar Series series.

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