Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments
Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments
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DOI：
10.1038/s41467-020-16972-5
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发表时间：
2020-06-19
影响因子：
16.6
通讯作者：
Lansky, Zdenek
中科院分区：
文献类型：
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作者：
Henrichs, Verena;Grycova, Lenka;Lansky, Zdenek
细胞器的细胞内运输由沿着微管步进的驱动蛋白-1 驱动，支撑着重要的细胞过程。在微管表面不存在其他蛋白质的情况下，驱动蛋白-1 执行微米长的运行。然而，在拥挤的条件下，kinesin-1 的运动会受到严重阻碍。因此，目前尚不清楚驱动蛋白-1 如何在细胞内环境中充当有效的转运蛋白。在这里，我们证明 TRAK1 (Milton) 是线粒体运输所必需的接头蛋白，可激活驱动蛋白-1 并提高驱动蛋白-1 在拥挤的微管表面上行走的稳健性。与 TRAK1 的相互作用 i) 促进 kinesin-1 绕过障碍物导航，ii) 增加 kinesin-1 通过 tau 粘性岛的概率，iii) 增加 kinesin-1 在细胞裂解液中的游程长度。我们通过观察到 TRAK1 与微管的直接相互作用解释了运动性的增强，为驱动蛋白-1-TRAK1 复合物提供了额外的锚点。此外，TRAK1 能够实现体外线粒体运输。我们提出适配器介导的束缚作为调节各种细胞环境中的驱动蛋白-1 运动的机制。细胞器的细胞内运输是由驱动蛋白 1 沿着微管步进驱动的，但拥挤的条件会阻碍驱动蛋白 1 的运动。作者在此证明，TRAK1（一种线粒体运输所必需的接头蛋白）可激活驱动蛋白-1，并提高驱动蛋白-1 在拥挤的微管表面上行走的稳健性。
Intracellular trafficking of organelles, driven by kinesin-1 stepping along microtubules, underpins essential cellular processes. In absence of other proteins on the microtubule surface, kinesin-1 performs micron-long runs. Under crowding conditions, however, kinesin-1 motility is drastically impeded. It is thus unclear how kinesin-1 acts as an efficient transporter in intracellular environments. Here, we demonstrate that TRAK1 (Milton), an adaptor protein essential for mitochondrial trafficking, activates kinesin-1 and increases robustness of kinesin-1 stepping on crowded microtubule surfaces. Interaction with TRAK1 i) facilitates kinesin-1 navigation around obstacles, ii) increases the probability of kinesin-1 passing through cohesive islands of tau and iii) increases the run length of kinesin-1 in cell lysate. We explain the enhanced motility by the observed direct interaction of TRAK1 with microtubules, providing an additional anchor for the kinesin-1-TRAK1 complex. Furthermore, TRAK1 enables mitochondrial transport in vitro. We propose adaptor-mediated tethering as a mechanism regulating kinesin-1 motility in various cellular environments. Intracellular trafficking of organelles is driven by kinesin-1 stepping along microtubules, but crowding conditions impede kinesin-1 motility. Here authors demonstrate that TRAK1, an adaptor protein essential for mitochondrial trafficking, activates kinesin-1 and increases robustness of kinesin-1 stepping on crowded microtubule surfaces.