Department of Biology, McGill University, Montréal, Quebec, Canada.
Department of Biophysics, University of Texas Southwestern, Dallas, TX, USA.
Nat Rev Mol Cell Biol. 2018 Jul;19(7):451-463. doi: 10.1038/s41580-018-0009-y.
Microtubules are dynamic polymers of αβ-tubulin that are essential for intracellular organization, organelle trafficking and chromosome segregation. Microtubule growth and shrinkage occur via addition and loss of αβ-tubulin subunits, which are biochemical processes. Dynamic microtubules can also engage in mechanical processes, such as exerting forces by pushing or pulling against a load. Recent advances at the intersection of biochemistry and mechanics have revealed the existence of multiple conformations of αβ-tubulin subunits and their central role in dictating the mechanisms of microtubule dynamics and force generation. It has become apparent that microtubule-associated proteins (MAPs) selectively target specific tubulin conformations to regulate microtubule dynamics, and mechanical forces can also influence microtubule dynamics by altering the balance of tubulin conformations. Importantly, the conformational states of tubulin dimers are likely to be coupled throughout the lattice: the conformation of one dimer can influence the conformation of its nearest neighbours, and this effect can propagate over longer distances. This coupling provides a long-range mechanism by which MAPs and forces can modulate microtubule growth and shrinkage. These findings provide evidence that the interplay between biochemistry and mechanics is essential for the cellular functions of microtubules.
微管是由αβ-微管蛋白组成的动态聚合物,对于细胞内组织、细胞器运输和染色体分离至关重要。微管的生长和收缩是通过αβ-微管蛋白亚基的添加和丢失来实现的,这是一个生化过程。动态微管还可以参与机械过程,例如通过推或拉对负载施加力。生物化学和力学交叉领域的最新进展揭示了αβ-微管蛋白亚基存在多种构象,它们在决定微管动力学和力产生机制方面起着核心作用。显然,微管相关蛋白(MAPs)选择性地针对特定的微管构象来调节微管动力学,机械力也可以通过改变微管构象的平衡来影响微管动力学。重要的是,微管二聚体的构象状态可能在晶格中相互关联:一个二聚体的构象可以影响其最近邻的构象,这种效应可以在更长的距离上传播。这种关联提供了一种长程机制,通过该机制,MAPs 和力可以调节微管的生长和收缩。这些发现为生物化学和力学之间的相互作用对于微管的细胞功能是必不可少的提供了证据。