Autoamplification and Competition Drive Symmetry Breaking

Initiation of Centriole Duplication by the PLK4-STIL Network

Marcin Leda, Andrew Holland, Andrew B. Goryachev

Research output: Contribution to journalArticle

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 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 (US)
Pages (from-to)222-235
Number of pages14
JournalFood Science and Human Wellness
Volume8
DOIs
StatePublished - Oct 26 2018

Fingerprint

Centrioles
centrioles
centrosomes
Centrosome
Cilia
mechanistic models
cilia
cell cycle
inheritance (genetics)
Cell Cycle
phosphotransferases (kinases)
Phosphotransferases
degradation

Keywords

  • Biological Sciences
  • Developmental Biology
  • In Silico Biology

ASJC Scopus subject areas

  • Food Science
  • General

Cite this

Autoamplification and Competition Drive Symmetry Breaking : Initiation of Centriole Duplication by the PLK4-STIL Network. / Leda, Marcin; Holland, Andrew; Goryachev, Andrew B.

In: Food Science and Human Wellness, Vol. 8, 26.10.2018, p. 222-235.

Research output: Contribution to journalArticle

@article{a79ddde86bea4400b29a7e6cf6ae00b5,
title = "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 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.",
keywords = "Biological Sciences, Developmental Biology, In Silico Biology",
author = "Marcin Leda and Andrew Holland and Goryachev, {Andrew B.}",
year = "2018",
month = "10",
day = "26",
doi = "10.1016/j.isci.2018.10.003",
language = "English (US)",
volume = "8",
pages = "222--235",
journal = "Food Science and Human Wellness",
issn = "2213-4530",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Autoamplification and Competition Drive Symmetry Breaking

T2 - Initiation of Centriole Duplication by the PLK4-STIL Network

AU - Leda, Marcin

AU - Holland, Andrew

AU - Goryachev, Andrew B.

PY - 2018/10/26

Y1 - 2018/10/26

N2 - 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.

AB - 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.

KW - Biological Sciences

KW - Developmental Biology

KW - In Silico Biology

UR - http://www.scopus.com/inward/record.url?scp=85056818022&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056818022&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2018.10.003

DO - 10.1016/j.isci.2018.10.003

M3 - Article

VL - 8

SP - 222

EP - 235

JO - Food Science and Human Wellness

JF - Food Science and Human Wellness

SN - 2213-4530

ER -