Regulation of microtubule-associated motors drives intermediate filament network polarization.
Regulation of microtubule-associated motors drives intermediate filament network polarization.
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DOI：
10.1083/jcb.201607045
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发表时间：
2017-06-05
期刊：
影响因子：
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通讯作者：
Etienne-Manneville S
中科院分区：
文献类型：
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作者：
Leduc C;Etienne-Manneville S
中间纤维（IF）参与定向细胞迁移，但IF网络如何在运动细胞中极化尚不清楚。Leduc和Etienne-Manneville表明，IF的周转主要依赖于肌动蛋白驱动的逆行流动和微管驱动的顺行和逆行运输。在细胞迁移过程中，Cdc 42介导的极性信号抑制动力蛋白依赖性转运，促进IF网络的极化。中间纤维（IF）是控制细胞形态和结构以及细胞极化、迁移和机械反应等活动过程的关键参与者。然而，控制IF动力学和运动细胞中的组织的调节机制仍然知之甚少。在这项研究中，我们调查的机制，导致极化重排的IF网络沿着极性轴。使用在表达波形蛋白，胶质细胞酸性蛋白，和巢蛋白的胶质细胞中的光漂白和光转换实验，我们表明，细胞质IFs的分布的结果从一个连续的营业额的基础上的合作肌动蛋白依赖的逆行流动和顺行和逆行微管依赖的运输。在创伤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方向偏移。这种转运的不对称性主要是由Cdc 42和非典型PKC依赖性抑制动力蛋白依赖性逆行转运引起的。我们的研究结果表明极性信号如何影响IF网络的动态周转，以促进网络本身的极化。
Intermediate filaments (IFs) participate in directed cell migration, but how the IF network becomes polarized in motile cells is unclear. Leduc and Etienne-Manneville show that the turnover of IF mainly relies on actin-driven retrograde flow and microtubule-driven anterograde and retrograde transport. During cell migration, Cdc42-mediated polarity signaling inhibits dynein-dependent transport to promote the polarization of the IF network. 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.