Rodriguez Josana, Peglion Florent, Martin Jack, Hubatsch Lars, Reich Jacob, Hirani Nisha, Gubieda Alicia G, Roffey Jon, Fernandes Artur Ribeiro, St Johnston Daniel, Ahringer Julie, Goehring Nathan W
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Wellcome Trust/Cancer Research UK Gurdon Institute, Cambridge CB2 1QN, UK.
The Francis Crick Institute, London NW1 1AT, UK.
Dev Cell. 2017 Aug 21;42(4):400-415.e9. doi: 10.1016/j.devcel.2017.07.007. Epub 2017 Aug 3.
The conserved polarity effector proteins PAR-3, PAR-6, CDC-42, and atypical protein kinase C (aPKC) form a core unit of the PAR protein network, which plays a central role in polarizing a broad range of animal cell types. To functionally polarize cells, these proteins must activate aPKC within a spatially defined membrane domain on one side of the cell in response to symmetry-breaking cues. Using the Caenorhabditis elegans zygote as a model, we find that the localization and activation of aPKC involve distinct, specialized aPKC-containing assemblies: a PAR-3-dependent assembly that responds to polarity cues and promotes efficient segregation of aPKC toward the anterior but holds aPKC in an inactive state, and a CDC-42-dependent assembly in which aPKC is active but poorly segregated. Cycling of aPKC between these distinct functional assemblies, which appears to depend on aPKC activity, effectively links cue-sensing and effector roles within the PAR network to ensure robust establishment of polarity.
保守的极性效应蛋白PAR-3、PAR-6、CDC-42和非典型蛋白激酶C（aPKC）形成了PAR蛋白网络的核心单元，该网络在多种动物细胞类型的极化过程中发挥着核心作用。为了使细胞功能极化，这些蛋白必须响应对称性破坏信号，在细胞一侧的空间限定膜结构域内激活aPKC。以秀丽隐杆线虫受精卵为模型，我们发现aPKC的定位和激活涉及不同的、专门的含aPKC组件：一种依赖PAR-3的组件，它响应极性信号并促进aPKC向前端有效分离，但使aPKC处于无活性状态；以及一种依赖CDC-42的组件，其中aPKC是活跃的，但分离效果不佳。aPKC在这些不同功能组件之间的循环，似乎依赖于aPKC的活性，有效地将PAR网络中的信号感知和效应作用联系起来，以确保极性的稳健建立。
