Nasrin Syeda Rubaiya, Ganser Christian, Nishikawa Seiji, Kabir Arif Md Rashedul, Sada Kazuki, Yamashita Takefumi, Ikeguchi Mitsunori, Uchihashi Takayuki, Hess Henry, Kakugo Akira
Faculty of Science, Hokkaido University, Sapporo, Hokkaido 060-0810, Japan.
Department of Creative Research, Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan.
Sci Adv. 2021 Oct 15;7(42):eabf2211. doi: 10.1126/sciadv.abf2211. Epub 2021 Oct 13.
Microtubules, the most rigid components of the cytoskeleton, can be key transduction elements between external forces and the cellular environment. Mechanical forces induce microtubule deformation, which is presumed to be critical for the mechanoregulation of cellular events. However, concrete evidence is lacking. In this work, with high-speed atomic force microscopy, we unravel how microtubule deformation regulates the translocation of the microtubule-associated motor protein kinesin-1, responsible for intracellular transport. Our results show that the microtubule deformation by bending impedes the translocation dynamics of kinesins along them. Molecular dynamics simulation shows that the hindered translocation of kinesins can be attributed to an enhanced affinity of kinesins to the microtubule structural units in microtubules deformed by bending. This study advances our understanding of the role of cytoskeletal components in mechanotransduction.
微管作为细胞骨架中最坚硬的成分,可能是外力与细胞环境之间的关键转导元件。机械力会引发微管变形,一般认为这对细胞活动的机械调节至关重要。然而,目前仍缺乏确凿证据。在这项研究中,我们借助高速原子力显微镜,揭示了微管变形是如何调节与微管相关的驱动蛋白1(负责细胞内运输)的转运过程的。我们的研究结果表明,弯曲导致的微管变形会阻碍驱动蛋白沿微管的转移动力学。分子动力学模拟显示,驱动蛋白转运受阻可归因于其对弯曲变形微管中微管结构单元的亲和力增强。这项研究增进了我们对细胞骨架成分在机械转导中作用的理解。