Par complex cluster formation mediated by phase separation
Authors: Jiawen Xu
Ying Mao
Yu Cai
Ziheng Liu
Weiguo Hu
Zhouhua Li
Haojie Lu
Mingjie Zhang
Wenyu Wen
Qun-Ying Lei
Ying Yang
Aihong Gu
Journal: Nature communications (2020)
Discipline: Multidisciplinary
Keywords: Par3; Par6; aPKC; cell cycle; condensation
Affiliations: Department of Neurosurgery, Huashan Hospital, the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China., Temasek Life Sciences Laboratory, Department of Biological Sciences, National University of Singapore, Singapore, 117604, Singapore., Fudan University Shanghai Cancer Center and Cancer Metabolism Laboratory, Fudan University, Shanghai, 200032, China., College of Life Sciences, Capital Normal University, Beijing, 100048, China., Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China., Temasek Life Sciences Laboratory, Department of Biological Sciences, National University of Singapore, Singapore, 117604, Singapore. ., Department of Neurosurgery, Huashan Hospital, the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. .

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. 

Retracted: No

PubPeer comments:
 Splicing in Figure 5A and 5B  , 
 #1 Pointless comment. The splice is readily apparent, and it has no impact on the experiment or the interpretation. , 
 Several points: 1. The splices, especially the second one, aren t as apparent in the smaller version of the figure that accompanies the text that most readers will see. 2. There is a reason that gel splicing is not allowed by most journals - because it does have an impact on the interpretation of the experiment. The same applies here. For example, there is no way to know whether the same contrast adjustments were applied to the spliced gels making it difficult or impossible to assess total loading across each of the experimental conditions. , 
 #3 RE: * aren t as apparent .* In the image at the journal the splice is much more clear than in the low-quality image posted above in #1. In both gels there is a thin white gap clearly evident. See here: https: www.nature.com articles s41467-020-16135-6 figures 5 RE: * ...there is no way to know whether the same contrast adjustments were applied to the spliced gels making it difficult or impossible to assess total loading across each of the experimental conditions. * Loading levels and contrast adjustments across the entire figure are irrelevant. The only relevant comparison is the pair-wise comparison of supernatant (S) vs. pellet (P) for each individual condition, to determine the percentage of protein that partitions into the pellet (as plotted in the charts below). It is clear that each pair is the same gel. Each pair could have been run on its own separate gel and the interpretation would not be affected. If you think otherwise, please explain precisely which of the authors interpretations is affected by the splice. (Hint: there aren t any.) ,