Autoamplification and Competition Drive Symmetry Breaking: Initiation of Centriole Duplication by the PLK4-STIL Network.

ABSTRACT: 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 compet

SUBMITTER: Leda M 

PROVIDER: S-EPMC6197440 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature