Department of Biochemistry, University of Geneva, Geneva, Switzerland; Department of Theoretical Physics, University of Geneva, Geneva, Switzerland.
Department of Biochemistry, University of Geneva, Geneva, Switzerland.
Biophys J. 2023 Jan 17;122(2):346-359. doi: 10.1016/j.bpj.2022.12.010. Epub 2022 Dec 9.
Control of microtubule abundance, stability, and length is crucial to regulate intracellular transport as well as cell polarity and division. How microtubule stability depends on tubulin addition or removal at the dynamic ends is well studied. However, microtubule rescue, the event when a microtubule switches from shrinking to growing, occurs at tubulin exchange sites along the shaft. Molecular motors have recently been shown to promote such exchanges. Using a stochastic theoretical description, we study how microtubule stability and length depend on motor-induced tubulin exchange and thus rescue. Our theoretical description matches our in vitro experiments on microtubule dynamics in the presence of kinesin-1 molecular motors. Although the overall dynamics of a population of microtubules can be captured by an effective rescue rate, by assigning rescue to exchange sites, we reveal that the dynamics of individual microtubules within the population differ dramatically. Furthermore, we study in detail a transition from bounded to unbounded microtubule growth. Our results provide novel insights into how molecular motors imprint information of microtubule stability on the microtubule network.
微管数量、稳定性和长度的控制对于调节细胞内运输以及细胞极性和分裂至关重要。微管动态末端的微管蛋白添加或去除如何影响微管稳定性已经得到了很好的研究。然而,微管挽救(当微管从收缩转变为生长时发生的事件)发生在轴上的微管交换部位。最近的研究表明,分子马达可以促进这种交换。我们使用随机理论描述来研究微管稳定性和长度如何取决于马达诱导的微管交换和挽救。我们的理论描述与我们在存在驱动蛋白-1 分子马达的情况下进行的体外微管动力学实验相匹配。尽管微管群体的整体动力学可以通过有效的挽救速率来捕捉,但通过将挽救分配给交换部位,我们揭示了群体中单个微管的动力学有很大差异。此外,我们详细研究了从有界到无界微管生长的转变。我们的结果为分子马达如何将微管稳定性的信息印在微管网络上提供了新的见解。