Matis Maja, Russler-Germain David A, Hu Qie, Tomlin Claire J, Axelrod Jeffrey D
Department of Pathology, Stanford University School of Medicine, Stanford, United States
Department of Pathology, Stanford University School of Medicine, Stanford, United States.
Elife. 2014 Aug 14;3:e02893. doi: 10.7554/eLife.02893.
Planar cell polarity (PCP) signaling controls the polarization of cells within the plane of an epithelium. Two molecular modules composed of Fat(Ft)/Dachsous(Ds)/Four-jointed(Fj) and a 'PCP-core' including Frizzled(Fz) and Dishevelled(Dsh) contribute to polarization of individual cells. How polarity is globally coordinated with tissue axes is unresolved. Consistent with previous results, we find that the Ft/Ds/Fj-module has an effect on a MT-cytoskeleton. Here, we provide evidence for the model that the Ft/Ds/Fj-module provides directional information to the core-module through this MT organizing function. We show Ft/Ds/Fj-dependent initial polarization of the apical MT-cytoskeleton prior to global alignment of the core-module, reveal that the anchoring of apical non-centrosomal MTs at apical junctions is polarized, observe that directional trafficking of vesicles containing Dsh depends on Ft, and demonstrate the feasibility of this model by mathematical simulation. Together, these results support the hypothesis that Ft/Ds/Fj provides a signal to orient core PCP function via MT polarization.
平面细胞极性(PCP)信号通路控制上皮平面内细胞的极化。由Fat(Ft)/Dachsous(Ds)/Four-jointed(Fj)组成的两个分子模块和一个包括Frizzled(Fz)和Dishevelled(Dsh)的“PCP核心”有助于单个细胞的极化。极性如何与组织轴进行全局协调仍未解决。与先前的结果一致,我们发现Ft/Ds/Fj模块对微管细胞骨架有影响。在这里,我们为Ft/Ds/Fj模块通过这种微管组织功能向核心模块提供方向信息的模型提供了证据。我们展示了在核心模块全局对齐之前,顶端微管细胞骨架的Ft/Ds/Fj依赖性初始极化,揭示了顶端非中心体微管在顶端连接处的锚定是极化的,观察到含有Dsh的囊泡的定向运输依赖于Ft,并通过数学模拟证明了该模型的可行性。总之,这些结果支持了Ft/Ds/Fj通过微管极化提供信号来定向核心PCP功能的假设。