Lawrence Elizabeth J, Chatterjee Saptarshi, Zanic Marija
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA.
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee, USA; Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee, USA; Department of Biochemistry, Vanderbilt University, Nashville, Tennessee, USA.
J Biol Chem. 2023 Dec;299(12):105398. doi: 10.1016/j.jbc.2023.105398. Epub 2023 Oct 28.
Microtubules are dynamic cytoskeletal filaments that undergo stochastic switching between phases of polymerization and depolymerization-a behavior known as dynamic instability. Many important cellular processes, including cell motility, chromosome segregation, and intracellular transport, require complex spatiotemporal regulation of microtubule dynamics. This coordinated regulation is achieved through the interactions of numerous microtubule-associated proteins (MAPs) with microtubule ends and lattices. Here, we review the recent advances in our understanding of microtubule regulation, focusing on results arising from biochemical in vitro reconstitution approaches using purified multiprotein ensembles. We discuss how the combinatory effects of MAPs affect both the dynamics of individual microtubule ends, as well as the stability and turnover of the microtubule lattice. In addition, we highlight new results demonstrating the roles of protein condensates in microtubule regulation. Our overall intent is to showcase how lessons learned from reconstitution approaches help unravel the regulatory mechanisms at play in complex cellular environments.
微管是动态的细胞骨架细丝，在聚合和解聚阶段之间经历随机切换——这种行为被称为动态不稳定性。许多重要的细胞过程，包括细胞运动、染色体分离和细胞内运输，都需要对微管动力学进行复杂的时空调节。这种协调调节是通过众多微管相关蛋白（MAPs）与微管末端和晶格的相互作用来实现的。在这里，我们回顾了我们对微管调节理解的最新进展，重点关注使用纯化的多蛋白组合进行生化体外重建方法所产生的结果。我们讨论了MAPs的组合效应如何影响单个微管末端的动力学，以及微管晶格的稳定性和更新。此外，我们强调了证明蛋白质凝聚物在微管调节中作用的新结果。我们的总体目的是展示从重建方法中学到的经验教训如何有助于揭示在复杂细胞环境中起作用的调节机制。
