Par complex cluster formation mediated by phase separation

Ziheng Liu, Ying Yang, Aihong Gu, Jiawen Xu, Ying Mao, Haojie Lu, Weiguo Hu, Qun-Ying Lei, Zhouhua Li, Mingjie Zhang, Yu Cai () and Wenyu Wen ()
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Ziheng Liu: Fudan University
Ying Yang: National University of Singapore
Aihong Gu: Fudan University
Jiawen Xu: Fudan University
Ying Mao: Fudan University
Haojie Lu: Fudan University
Weiguo Hu: Fudan University
Qun-Ying Lei: Fudan University
Zhouhua Li: Capital Normal University
Mingjie Zhang: Hong Kong University of Science and Technology
Yu Cai: National University of Singapore
Wenyu Wen: Fudan University

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-16135-6

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