Centre for BioSystems Science and Engineering , Indian Institute of Science , Bangalore 560012 , India.
Biochemistry. 2020 Jan 21;59(2):156-162. doi: 10.1021/acs.biochem.9b00772. Epub 2019 Oct 16.
Cytoplasmic dynein, the major minus end-directed motor protein in several cell types, transports a variety of intracellular cargo upon forming a processive tripartite complex with its activator dynactin and cargo adaptors such as Hook3 and BicD2. Our current understanding of dynein regulation stems from a combination of studies of cargo movement upon perturbation of dynein activity, single-molecule experiments, and cryo-electron microscopy studies of dynein structure and its interaction with dynactin and cargo adaptors. In this Perspective, we first consolidate data from recent publications to understand how perturbations to the dynein-dynactin interaction and dynactin's localization alter the behavior of dynein-driven cargo transport in a cell type- and experimental condition-specific manner. In addition, we touch upon results from and studies to elucidate how dynein's interaction with dynactin and cargo adaptors activates dynein and enhances its processivity. Finally, we propose questions that need to be addressed in the future with appropriate experimental designs so as to improve our understanding of the spatiotemporal regulation of dynein's function in the context of the distribution and dynamics of dynactin in living cells.
细胞质动力蛋白是几种细胞类型中主要的向负极方向运动的分子马达，它与激活因子 dynactin 以及货物衔接蛋白（如 Hook3 和 BicD2）形成连续的三元复合物，从而运输各种细胞内货物。我们对动力蛋白调节的理解源于对动力蛋白活性扰动后货物运动的研究、单分子实验以及动力蛋白结构及其与 dynactin 和货物衔接蛋白相互作用的冷冻电子显微镜研究的综合。在本观点中，我们首先整合了最近出版物中的数据，以了解 dynactin 相互作用和 dynactin 定位的扰动如何以细胞类型和实验条件特异性的方式改变动力蛋白驱动的货物运输行为。此外，我们还探讨了研究结果，以阐明动力蛋白与 dynactin 和货物衔接蛋白的相互作用如何激活动力蛋白并增强其连续性。最后，我们提出了未来需要通过适当的实验设计来解决的问题，以便提高我们对 dynactin 在活细胞中的分布和动力学背景下对动力蛋白功能的时空调节的理解。
