Bidirectional helical motility of cytoplasmic dynein around microtubules.
Bidirectional helical motility of cytoplasmic dynein around microtubules.
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DOI：
10.7554/elife.03205
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发表时间：
2014-07-28
期刊：
影响因子：
7.7
通讯作者：
Yildiz A
中科院分区：
文献类型：
--
作者：
Can S;Dewitt MA;Yildiz A
胞浆动力蛋白是一种分子马达，负责沿微管负端定向运输货物。动力蛋白的运动性已经在体外研究了表面固定化的MTS，这限制了马达在二维空间的运动。在这项研究中，我们使用MT电桥实验从三维角度探讨了动力蛋白的运动性。我们发现动力蛋白在MT周围以螺旋轨迹运动，表明它在货物运输过程中产生扭矩。与其他在特定方向上产生扭矩的细胞骨架马达不同，动力蛋白在两个方向上都会产生扭矩，从而导致双向螺旋运动。动力蛋白有一种沿着右旋螺旋路径移动的净偏好，这表明当采取侧向步骤时，头部倾向于在正向结合到最近的微管蛋白结合部位。这种双向螺旋运动可能使dynein在货物运输过程中避开密集细胞质环境中的路障。DOI：http://dx.doi.org/10.7554/eLife.03205.001细胞依靠“分子马达”沿着称为微管的轨道移动，在细胞的不同部分之间移动蛋白质和其他货物。动力蛋白是一种分子马达，它通过向微管轨迹缓慢生长的一端迈出一步来沿着这些微管移动。动力蛋白发动机的轨迹已经被广泛研究，使用的技术可以跟踪它们在两个维度上的运动。然而，一些分子马达也可以在移动时旋转，产生一种称为扭矩的扭转力，使马达以螺旋形式围绕微管旋转。为了评估动力蛋白可以产生的扭矩，并更好地理解它在三维中的运动，Can等人说。用一段微管在两个聚苯乙烯珠子之间架起了一座“桥梁”。动力蛋白发动机被制造成携带一个更小的聚苯乙烯珠子作为货物，并使用计算机算法来跟踪这个更小的珠子的运动，以解释显微镜记录的运动。Can等人。研究发现，动力蛋白在微管周围以螺旋轨迹运动，而不是沿微管直线运动。当它移动时，它可以向一个方向或另一个方向扭曲，在两个方向上都产生扭矩。这与其他类型的分子马达不同，分子马达只在一个方向上产生扭矩。然而，动力蛋白倾向于向右旋转，这表明沿着微管的每一步，它都会在正向与最近的可用结合部位结合。为什么分子马达以这种方式运行会很有用？Can等人。提出，在密集和繁忙的蜂窝环境中，双向旋转的能力可能会使Dynein避开路障或其他障碍。DOI：http://dx.doi.org/10.7554/eLife.03205.002
Cytoplasmic dynein is a molecular motor responsible for minus-end-directed cargo transport along microtubules (MTs). Dynein motility has previously been studied on surface-immobilized MTs in vitro, which constrains the motors to move in two dimensions. In this study, we explored dynein motility in three dimensions using an MT bridge assay. We found that dynein moves in a helical trajectory around the MT, demonstrating that it generates torque during cargo transport. Unlike other cytoskeletal motors that produce torque in a specific direction, dynein generates torque in either direction, resulting in bidirectional helical motility. Dynein has a net preference to move along a right-handed helical path, suggesting that the heads tend to bind to the closest tubulin binding site in the forward direction when taking sideways steps. This bidirectional helical motility may allow dynein to avoid roadblocks in dense cytoplasmic environments during cargo transport. DOI: http://dx.doi.org/10.7554/eLife.03205.001 Cells rely on ‘molecular motors’ travelling along tracks called microtubules to move proteins and other cargoes between different parts of a cell. Dynein is a molecular motor that moves along the microtubules by taking “steps” towards the slowly growing end of these tracks. The trajectories of dynein motors have been studied extensively using techniques that can follow their movements in two dimensions. However, some molecular motors can also rotate as they travel, creating a twisting force called a torque that causes the motor to spiral around the microtubule in a helix. To assess the torque that dynein can generate and to better understand its movements in three dimensions, Can et al. used a length of microtubule to build a ‘bridge’ between two polystyrene beads. The dynein motors were made to carry a smaller polystyrene bead as cargo, and the movement of this smaller bead was tracked using a computer algorithm to interpret the motion recorded by a microscope. Can et al. found that dynein moves in a helical trajectory around the microtubule, rather than travelling along it in a straight line. As it travels it can twist in one direction or the other, generating torque in either direction. This is unlike other types of molecular motor, which produce torque in just one direction. However, dynein prefers to rotate to the right, suggesting that with every step along a microtubule, it binds to the closest available binding site in the forward direction. Why might it be useful for molecular motors to behave in this way? Can et al. propose that the ability to rotate in both directions may allow dynein to avoid roadblocks or other obstacles in the dense and busy cellular environment in which it has to operate. DOI: http://dx.doi.org/10.7554/eLife.03205.002