Soundararajan Harish Chandra, Bullock Simon L
Division of Cell Biology, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
Elife. 2014 Apr 15;3:e01596. doi: 10.7554/eLife.01596.
Many cellular constituents travel along microtubules in association with multiple copies of motor proteins. How the activity of these motors is regulated during cargo sorting is poorly understood. In this study, we address this issue using a novel in vitro assay for the motility of localising Drosophila mRNAs bound to native dynein-dynactin complexes. High precision tracking reveals that individual RNPs within a population undergo either diffusive, or highly processive, minus end-directed movements along microtubules. RNA localisation signals stimulate the processive movements, with regulation of dynein-dynactin's activity rather than its total copy number per RNP, responsible for this effect. Our data support a novel mechanism for multi-motor translocation based on the regulation of dynein processivity by discrete cargo-associated features. Studying the in vitro responses of RNPs to microtubule-associated proteins (MAPs) and microtubule ends provides insights into how an RNA population could navigate the cytoskeletal network and become anchored at its destination in cells. DOI: http://dx.doi.org/10.7554/eLife.01596.001.
许多细胞成分与多个拷贝的运动蛋白结合,沿微管移动。在货物分拣过程中,这些运动蛋白的活性是如何被调控的,目前还知之甚少。在本研究中,我们使用一种新型体外分析方法,来研究与天然动力蛋白-动力蛋白激活蛋白复合物结合的定位果蝇mRNA的运动性,以此解决这一问题。高精度追踪显示,群体中的单个核糖核蛋白颗粒(RNP)会沿着微管进行扩散运动或高度持续性的、向负端的移动。RNA定位信号刺激持续性运动,动力蛋白-动力蛋白激活蛋白活性的调控而非每个RNP的总拷贝数,对此效应负责。我们的数据支持一种基于离散货物相关特征对动力蛋白持续性进行调控的新型多运动蛋白易位机制。研究RNP对微管相关蛋白(MAP)和微管末端的体外反应,有助于深入了解RNA群体如何在细胞骨架网络中导航并锚定在其细胞内目的地。DOI: http://dx.doi.org/10.7554/eLife.01596.001