Par complex cluster formation mediated by phase separation
Par complex cluster formation mediated by phase separation
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DOI：
10.1038/s41467-020-18162-9
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发表时间：
2020-05-08
影响因子：
16.6
通讯作者：
Wen, Wenyu
中科院分区：
文献类型：
--
作者：
Liu, Ziheng;Yang, Ying;Wen, Wenyu
进化上保守的Par 3/Par 6/aPKC复合物调节不同细胞类型的极性建立和不同的极性驱动功能。然而，Par复合物如何在膜下浓缩以启动细胞极化仍不清楚。在这里，我们表明，Par复合物表现出细胞周期依赖的凝聚在果蝇神经母细胞，驱动液-液相分离。开放构象的Par 3经历自主相分离可能是由于其NTD介导的寡聚化。Par 6通过C-末端尾部结合到Par 3 PDZ 3上，可以富集到Par 3缩合物中，并反过来显著促进Par 3相分离。aPKC也可以作为客户浓缩成Par 3 N/Par 6缩合物。有趣的是，活化的aPKC可以通过Par 3的磷酸化分散Par 3/Par 6缩合物。Par 3/Par 6相分离的扰动损害了成神经细胞不对称分裂过程中顶端-基底极性的建立，并导致有缺陷的谱系发育。我们建议，相分离可能是一个共同的机制，局部皮质凝聚细胞极性复合物。进化上保守的复合物，Par蛋白，调节细胞极性。在这里，作者表明，在果蝇神经母细胞中，Par复合物表现出依赖于细胞周期的液-液相分离。
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. The evolutionarily conserved complex, the Par proteins, regulates cell polarity. Here, the authors show that in Drosophila neuroblasts, the Par complex exhibits liquid-liquid phase separation dependent on the cell cycle.