Autoinhibition and cooperative activation mechanisms of cytoplasmic dynein
Autoinhibition and cooperative activation mechanisms of cytoplasmic dynein
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DOI：
10.1038/ncb3048
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发表时间：
2014-11-01
影响因子：
21.3
通讯作者：
Furuta, Ken'ya
中科院分区：
文献类型：
--
作者：
Torisawa, Takayuki;Ichikawa, Muneyoshi;Furuta, Ken'ya
细胞质动力蛋白是一种基于双头微管的马达，负责多种细胞内运动，包括细胞器的负端定向运输(1-3)。货物运输车的机动性根据货物的存在或不存在进行调节（4-6）；然而，目前尚不清楚细胞质动力蛋白如何实现这种调节。在这里，我们在体外使用重组和天然动力蛋白复合物，表明单独的单个动力蛋白分子处于自动抑制状态，其中两个运动头堆叠在一起。在这种状态下，动力蛋白沿着微管扩散移动，仅向微管的负端有很小的偏向。当两个头被一根刚性杆物理分开时，动力蛋白分子的运动变得定向和持续。此外，在单个货物上组装多个动力蛋白分子使它们能够单向移动并协同产生力。因此，我们提出了一种货物运输的自主开关机制，其中细胞中的单个动力蛋白分子通过分子内头-头堆积而被自动抑制，并在它们作为一个团队在货物上组装时变得活跃。
Cytoplasmic dynein is a two-headed microtubule-based motor responsible for diverse intracellular movements, including minus-end-directed transport of organelles(1-3). The motility of cargo transporters is regulated according to the presence or absence of cargo(4-6); however, it remains unclear how cytoplasmic dynein achieves such regulation. Here, using a recombinant and native dynein complex in vitro, we show that lone, single dynein molecules are in an autoinhibited state, in which the two motor heads are stacked together. In this state, dynein moves diffusively along a microtubule with only a small bias towards the minus end of the microtubule. When the two heads were physically separated by a rigid rod, the movement of dynein molecules became directed and processive. Furthermore, assembly of multiple dynein molecules on a single cargo enabled them to move unidirectionally and generate force cooperatively. We thus propose a mechanism of autonomous on-off switching of cargo transport, in which single dynein molecules in the cell are autoinhibited through intramolecular head-head stacking and become active when they assemble as a team on a cargo.