Autoamplification and competition drive symmetry breaking: Initiation of centriole duplication by the PLK4-STIL network

Marcin Leda, Andrew J. Holland, Andrew B. Goryachev

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)222-235
Number of pages24
JournaliScience
Volume8
Early online date11 Oct 2018
DOIs
Publication statusPublished - 26 Oct 2018

Keywords / Materials (for Non-textual outputs)

  • Biological Sciences
  • Developmental Biology
  • In Silico Biology

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