Leduc Cécile, Etienne-Manneville Sandrine
Institut Pasteur Paris, Cell Polarity, Migration and Cancer Unit, UMR 3691, Equipe Labellisée Ligue Contre le Cancer, Centre National de la Recherché Scientifique, 75724 Paris, France.
J Cell Biol. 2017 Jun 5;216(6):1689-1703. doi: 10.1083/jcb.201607045. Epub 2017 Apr 21.
Intermediate filaments (IFs) are key players in the control of cell morphology and structure as well as in active processes such as cell polarization, migration, and mechanoresponses. However, the regulatory mechanisms controlling IF dynamics and organization in motile cells are still poorly understood. In this study, we investigate the mechanisms leading to the polarized rearrangement of the IF network along the polarity axis. Using photobleaching and photoconversion experiments in glial cells expressing vimentin, glial fibrillary acidic protein, and nestin, we show that the distribution of cytoplasmic IFs results from a continuous turnover based on the cooperation of an actin-dependent retrograde flow and anterograde and retrograde microtubule-dependent transports. During wound-induced astrocyte polarization, IF transport becomes directionally biased from the cell center toward the cell front. Such asymmetry in the transport is mainly caused by a Cdc42- and atypical PKC-dependent inhibition of dynein-dependent retrograde transport. Our results show how polarity signaling can affect the dynamic turnover of the IF network to promote the polarization of the network itself.
中间丝(IFs)在控制细胞形态和结构以及细胞极化、迁移和机械反应等活跃过程中起着关键作用。然而,控制运动细胞中IF动态和组织的调节机制仍知之甚少。在本研究中,我们研究了导致IF网络沿极性轴进行极化重排的机制。通过在表达波形蛋白、胶质纤维酸性蛋白和巢蛋白的胶质细胞中进行光漂白和光转换实验,我们表明细胞质IFs的分布源于基于肌动蛋白依赖性逆行流与顺行和逆行微管依赖性运输协同作用的持续周转。在伤口诱导的星形胶质细胞极化过程中,IF运输从细胞中心向细胞前端呈现出方向偏向性。这种运输的不对称主要是由Cdc42和非典型蛋白激酶C依赖性抑制动力蛋白依赖性逆行运输引起的。我们的结果表明极性信号如何影响IF网络的动态周转以促进网络自身的极化。