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Regulation of microtubule dynamics, mechanics and function through the growing tip
Nature Reviews Molecular Cell Biology ( IF 112.7 ) Pub Date : 2021-08-18 , DOI: 10.1038/s41580-021-00399-x
Nikita B Gudimchuk 1, 2, 3 , J Richard McIntosh 4
Affiliation  

Microtubule dynamics and their control are essential for the normal function and division of all eukaryotic cells. This plethora of functions is, in large part, supported by dynamic microtubule tips, which can bind to various intracellular targets, generate mechanical forces and couple with actin microfilaments. Here, we review progress in the understanding of microtubule assembly and dynamics, focusing on new information about the structure of microtubule tips. First, we discuss evidence for the widely accepted GTP cap model of microtubule dynamics. Next, we address microtubule dynamic instability in the context of structural information about assembly intermediates at microtubule tips. Three currently discussed models of microtubule assembly and dynamics are reviewed. These are considered in the context of established facts and recent data, which suggest that some long-held views must be re-evaluated. Finally, we review structural observations about the tips of microtubules in cells and describe their implications for understanding the mechanisms of microtubule regulation by associated proteins, by mechanical forces and by microtubule-targeting drugs, prominently including cancer chemotherapeutics.



中文翻译:

通过生长尖端调节微管动力学、力学和功能

微管动力学及其控制对于所有真核细胞的正常功能和分裂至关重要。这种过多的功能在很大程度上得到了动态微管尖端的支持,微管尖端可以与各种细胞内靶标结合,产生机械力并与肌动蛋白微丝结合。在这里,我们回顾了在理解微管组装和动力学方面的进展,重点关注有关微管尖端结构的新信息。首先,我们讨论了广泛接受的微管动力学 GTP 帽模型的证据。接下来,我们在有关微管尖端组装中间体的结构信息的背景下解决微管动态不稳定性。回顾了目前讨论的三种微管组装和动力学模型。这些是在既定事实和最近数据的背景下考虑的,这表明必须重新评估一些长期持有的观点。最后,我们回顾了关于细胞中微管尖端的结构观察,并描述了它们对理解相关蛋白、机械力和微管靶向药物(主要包括癌症化疗药物)对微管调节机制的影响。

更新日期:2021-08-19
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