Par complex cluster formation mediated by phase separation

Nat Commun. 2020 May 8;11(1):2266. doi: 10.1038/s41467-020-16135-6.

Abstract

The evolutionarily conserved Par3/Par6/aPKC complex regulates the polarity establishment of diverse cell types and distinct polarity-driven functions. However, how the Par complex is concentrated beneath the membrane to initiate cell polarization remains unclear. Here we show that the Par complex exhibits cell cycle-dependent condensation in Drosophila neuroblasts, driven by liquid-liquid phase separation. The open conformation of Par3 undergoes autonomous phase separation likely due to its NTD-mediated oligomerization. Par6, via C-terminal tail binding to Par3 PDZ3, can be enriched to Par3 condensates and in return dramatically promote Par3 phase separation. aPKC can also be concentrated to the Par3N/Par6 condensates as a client. Interestingly, activated aPKC can disperse the Par3/Par6 condensates via phosphorylation of Par3. Perturbations of Par3/Par6 phase separation impair the establishment of apical-basal polarity during neuroblast asymmetric divisions and lead to defective lineage development. We propose that phase separation may be a common mechanism for localized cortical condensation of cell polarity complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Cycle
  • Cell Differentiation
  • Cell Survival
  • Chlorocebus aethiops
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / metabolism*
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Larva / cytology
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism*
  • Neurons / cytology
  • Neurons / metabolism
  • Protein Domains
  • Protein Kinase C / metabolism
  • Rats

Substances

  • Drosophila Proteins
  • Multiprotein Complexes
  • Green Fluorescent Proteins
  • Protein Kinase C