University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
J Cell Sci. 2019 Mar 15;132(6):jcs227132. doi: 10.1242/jcs.227132.
Cytoplasmic dynein-1 (hereafter dynein) is an essential cellular motor that drives the movement of diverse cargos along the microtubule cytoskeleton, including organelles, vesicles and RNAs. A long-standing question is how a single form of dynein can be adapted to a wide range of cellular functions in both interphase and mitosis. Recent progress has provided new insights - dynein interacts with a group of activating adaptors that provide cargo-specific and/or function-specific regulation of the motor complex. Activating adaptors such as BICD2 and Hook1 enhance the stability of the complex that dynein forms with its required activator dynactin, leading to highly processive motility toward the microtubule minus end. Furthermore, activating adaptors mediate specific interactions of the motor complex with cargos such as Rab6-positive vesicles or ribonucleoprotein particles for BICD2, and signaling endosomes for Hook1. In this Cell Science at a Glance article and accompanying poster, we highlight the conserved structural features found in dynein activators, the effects of these activators on biophysical parameters, such as motor velocity and stall force, and the specific intracellular functions they mediate.
细胞质动力蛋白-1（以下简称动力蛋白）是一种重要的细胞马达，能够沿着微管细胞骨架驱动各种货物的运动，包括细胞器、囊泡和 RNA。一个长期存在的问题是，单一形式的动力蛋白如何适应有丝分裂和间期的多种细胞功能。最近的研究进展提供了新的见解——动力蛋白与一组激活适配器相互作用，为马达复合物提供货物特异性和/或功能特异性调节。激活适配器，如 BICD2 和 Hook1，增强了动力蛋白与其必需激活因子 dynactin 形成的复合物的稳定性，从而导致向微管负端的高连续性运动。此外，激活适配器介导马达复合物与货物的特异性相互作用，如 BICD2 与 Rab6 阳性囊泡或核糖核蛋白颗粒，以及 Hook1 与信号内体。在这篇《细胞科学概览》文章及其配套海报中，我们重点介绍了动力蛋白激活剂中发现的保守结构特征、这些激活剂对生物物理参数的影响，例如马达速度和停顿力，以及它们介导的特定细胞内功能。
