Projects per year
Centrioles, the cores of centrosomes and cilia, duplicate every cell cycle to ensure their faithful inheritance. How only a single procentriole is produced on each mother centriole remains enigmatic. We propose the first mechanistic biophysical model for procentriole initiation which posits that interactions between kinase PLK4 and its activator-substrate STIL are central for procentriole initiation. The model recapitulates the transition from a uniform "ring" of PLK4 surrounding the mother centriole to a single PLK4 "spot" that initiates procentriole assembly. This symmetry breaking requires autocatalytic activation of PLK4 and enhanced centriolar anchoring of PLK4 by phosphorylated STIL. We find that in situ degradation of active PLK4 cannot break symmetry. The model predicts that competition between transient PLK4 activity maxima for PLK4-STIL complexes destabilizes the PLK4 ring and produces instead a single PLK4 spot. Weakening of competition by overexpression of PLK4 and STIL causes progressive addition of supernumerary procentrioles, as observed experimentally.
- Biological Sciences
- Developmental Biology
- In Silico Biology
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- 2 Finished
15 NSFBIO: Excitocell: A rewired eukaryotic cell model for the analysis and design of cellular morphogenesis
1/11/17 → 31/12/20
Cortical excitability as a mechanism for epithelial barrier maintenance: A joint experiment-theory systems approach
26/06/17 → 25/06/20