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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Tug-of-war between dissimilar teams of microtubule motors regulates transport and fission of endosomes
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Tug-of-war between dissimilar teams of microtubule motors regulates transport and fission of endosomes

机译：微管马达的不同团队之间的拔河比赛调节了内体的运输和裂变

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Intracellular transport is interspersed with frequent reversals in direction due to the presence of opposing kinesin and dynein motors on organelles that are carried as cargo. The cause and the mechanism of reversals are unknown, but are a key to understanding how cargos are delivered in a regulated manner to specific cellular locations. Unlike established single-motor biophysical assays, this problem requires understanding of the cooperative behavior of multiple interacting motors. Here we present measurements inside live Dictyostelium cells, in a cell extract and with purified motors to quantify such an ensemble function of motors. We show through precise motion analysis that reversals during endosome motion are caused by a tug-of-war between kinesin and dynein. Further, we use a combination of optical trap-based force measurements and Monte Carlo simulations to make the surprising discovery that endosome transport uses many (approximately four to eight) weak and detachment-prone dyneins in a tug-of-war against a single strong and tenacious kinesin. We elucidate how this clever choice of dissimilar motors and motor teams achieves net transport together with endosome fission, both of which are important in controlling the balance of endocytic sorting. To the best of our knowledge, this is a unique demonstration that dynein and kinesin function differently at the molecular level inside cells and of how this difference is used in a specific cellular process, namely endosome biogenesis. Our work may provide a platform to understand intracellular transport of a variety of organelles in terms of measurable quantities.
机译：由于在作为货物运输的细胞器上存在相反的驱动蛋白和动力蛋白马达，细胞内的运输散布着频繁的方向反转。逆转的原因和机理尚不清楚，但这是了解如何以受控方式将货物运送到特定蜂窝位置的关键。与已建立的单马达生物物理测定法不同，此问题需要了解多个相互作用马达的协同行为。在这里，我们介绍了活的Dictyostelium细胞内部，细胞提取物中以及纯化的电动机中的测量结果，以量化电动机的这种整体功能。我们通过精确的运动分析表明，内体运动过程中的逆转是由驱动蛋白和动力蛋白之间的拔河引起的。此外，我们结合使用了基于光阱的力测量结果和蒙特卡洛模拟，得出令人惊讶的发现，即内体运输在一次拔河中对单个强力使用了许多（大约4到8个）弱和易分离的动力蛋白。和顽强的驱动蛋白。我们阐明了这种异类电机和电机团队的明智选择如何实现净运输和内体裂变，这两者对于控制内吞分选的平衡都很重要。据我们所知，这是独特的证明，动力蛋白和驱动蛋白在细胞内的分子水平上具有不同的功能，并且这种差异如何用于特定的细胞过程，即内体生物发生。我们的工作可能提供一个平台，以可测量的数量了解各种细胞器的细胞内运输。

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