Microtubules tightly regulate various cellular activities. Our understanding of microtubules is largely based on experiments using microtubule-targeting agents, which, however, are insufficient to dissect the dynamic mechanisms of specific microtubule populations, due to their slow effects on the entire pool of microtubules. To overcome this technological limitation, we have used chemo and optogenetics to disassemble specific microtubule subtypes, including tyrosinated microtubules, primary cilia, mitotic spindles, and intercellular bridges, by rapidly recruiting engineered microtubule-cleaving enzymes onto target microtubules in a reversible manner. Using this approach, we show that acute microtubule disassembly swiftly halts vesicular trafficking and lysosomal dynamics. It also immediately triggers Golgi and ER reorganization and slows the fusion/fission of mitochondria without affecting mitochondrial membrane potential. In addition, cell rigidity is increased after microtubule disruption owing to increased contractile stress fibers. Microtubule disruption furthermore prevents cell division, but does not cause cell death during interphase. Overall, the reported tools facilitate detailed analysis of how microtubules precisely regulate cellular architecture and functions.

中文翻译：

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精确控制活细胞中微管的分解


微管严格调节各种细胞活动。我们对微管的理解很大程度上基于使用微管靶向剂的实验，然而，由于它们对整个微管库的缓慢影响，这些实验不足以剖析特定微管群体的动态机制。为了克服这一技术限制，我们使用化学和光遗传学来分解特定的微管亚型，包括酪氨酸微管、初级纤毛、有丝分裂纺锤体和细胞间桥，通过以可逆的方式快速将工程微管切割酶招募到目标微管上。使用这种方法，我们表明急性微管分解迅速停止囊泡运输和溶酶体动力学。它还立即触发高尔基体和内质网重组，并减慢线粒体的融合/裂变，而不影响线粒体膜电位。此外，由于收缩应力纤维增加，微管破坏后细胞刚性增加。微管破坏还可以防止细胞分裂，但不会导致间期细胞死亡。总体而言，所报道的工具有助于详细分析微管如何精确调节细胞结构和功能。