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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Biophysics

Background:

  • The Par3/Par6/aPKC complex is essential for establishing cell polarity.
  • Mechanisms of cortical concentration for initiating cell polarization are not fully understood.

Purpose of the Study:

  • To investigate how the Par complex concentrates at the membrane to initiate cell polarization.
  • To elucidate the role of liquid-liquid phase separation in Par complex organization.

Main Methods:

  • Studied cell cycle-dependent condensation of the Par complex in Drosophila neuroblasts.
  • Investigated the biophysical properties of Par3, Par6, and aPKC interactions.
  • Utilized perturbations to assess the impact on polarity and development.

Main Results:

  • The Par complex undergoes cell cycle-dependent condensation driven by liquid-liquid phase separation.
  • Par3's open conformation self-condenses, promoted by Par6 binding.
  • Activated aPKC disperses condensates via Par3 phosphorylation, while it is concentrated as a client.
  • Disruption of phase separation impairs apical-basal polarity and neuroblast lineage development.

Conclusions:

  • Liquid-liquid phase separation drives the condensation of the Par complex for cell polarization.
  • This mechanism is critical for asymmetric cell division and development.
  • Phase separation may be a general principle for cortical condensation of polarity complexes.