Multimotor Transport in a System of Active and Inactive Kinesin-1 Motors
Multimotor Transport in a System of Active and Inactive Kinesin-1 Motors
复制标题
DOI：
10.1016/j.bpj.2014.06.014
复制
发表时间：
2014-07-15
影响因子：
3.4
通讯作者：
Diez, Stefan
中科院分区：
文献类型：
--
作者：
Scharrel, Lara;Ma, Rui;Diez, Stefan
基于微管的运动蛋白促进细胞内的长程定向运输。一个例子是神经细胞中的运输，其中一小组运动蛋白（例如驱动蛋白和细胞质动力蛋白）一起工作，以确保沿着轴突的细胞物质的供应和清除。轴突运输缺陷与阿尔茨海默病和其他神经退行性疾病有关。然而，如果一小部分电机有缺陷，目前尚不清楚基于多电机的货物运输如何受到损害。为了在体外模拟受损的多传感器运输，我们用不同比例的活性 kinesin-1 马达和非活性 kinesin-1 马达突变体进行了滑行运动测定。我们发现受损的运输表现在多种运动状态中：1）快速运动状态，其特征是以接近主动马达的单分子速度的速度滑行； 2)、以接近零速度或完全停止的滑翔为特征的慢速运动状态； 3）快速运动和慢速运动并存的状态。值得注意的是，从快速状态到慢速状态的转变在活跃电机的阈值部分急剧发生。基于单电机参数，我们开发了一个随机模型和平均场理论描述来解释我们的实验结果。我们的结果表明，受损的多传感器传输大多以非此即彼的方式发生：根据活动电机与非活动电机的比例，传输要么以接近全速进行，要么停止运行。
Long-range directional transport in cells is facilitated by nnicrotubule-based motor proteins. One example is transport in a nerve cell, where small groups of motor proteins, such as kinesins and cytoplasmic dynein, work together to ensure the supply and clearance of cellular material along the axon. Defects in axonal transport have been linked to Alzheimer's and other neurodegenerative diseases. However, it is not known in detail how multimotor-based cargo transport is impaired if a fraction of the motors are defective. To mimic impaired multinnotor transport in vitro, we performed gliding motility assays with varying fractions of active kinesin-1 motors and inactive kinesin-1 motor mutants. We found that impaired transport manifests in multiple motility regimes: 1), a fast-motility regime characterized by gliding at velocities close to the single-molecule velocity of the active motors; 2), a slow-motility regime characterized by gliding at close-to zero velocity or full stopping; and 3), a regime in which fast and slow motilities coexist. Notably, the transition from the fast to the slow regime occurred sharply at a threshold fraction of active motors. Based on single-motor parameters, we developed a stochastic model and a mean-field theoretical description that explain our experimental findings. Our results demonstrate that impaired multinnotor transport mostly occurs in an either/or fashion: depending on the ratio of active to inactive motors, transport is either performed at close to full speed or is out of action.