Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, Texas, USA; and.
FASEB J. 2019 Jan;33(1):388-399. doi: 10.1096/fj.201800604R. Epub 2018 Jun 26.
Keratin intermediate filaments (IFs) are the major cytoskeletal component in epithelial cells. The dynamics of keratin IFs have been described to depend mostly on the actin cytoskeleton, but the rapid transport of fully polymerized keratin filaments has not been reported. In this work, we used a combination of photoconversion experiments and clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated protein 9 genome editing to study the role of microtubules and microtubule motors in keratin filament transport. We found that long keratin filaments, like other types of IFs, are transported along microtubules by kinesin-1. Our data revealed that keratin and vimentin are nonconventional kinesin-1 cargoes because their transport did not require kinesin light chains, which are a typical adapter for kinesin-dependent cargo transport. Furthermore, we found that the same domain of the kinesin heavy chain tail is involved in keratin and vimentin IF transport, strongly suggesting that multiple types of IFs move along microtubules using an identical mechanism.-Robert, A., Tian, P., Adam, S. A., Kittisopikul, M., Jaqaman, K., Goldman, R. D., Gelfand, V. I. Kinesin-dependent transport of keratin filaments: a unified mechanism for intermediate filament transport.
角蛋白中间丝(IFs)是上皮细胞中主要的细胞骨架成分。角蛋白 IF 的动力学主要依赖于肌动蛋白细胞骨架,但完全聚合的角蛋白丝的快速运输尚未被报道。在这项工作中,我们使用光转化实验和簇状规则间隔短回文重复/簇状规则间隔短回文重复相关蛋白 9 基因组编辑的组合来研究微管和微管马达在角蛋白丝运输中的作用。我们发现,长角蛋白丝与其他类型的 IF 一样,通过驱动蛋白-1 沿微管运输。我们的数据表明,角蛋白和波形蛋白是非典型的驱动蛋白-1 货物,因为它们的运输不需要驱动蛋白轻链,而驱动蛋白轻链是驱动蛋白依赖性货物运输的典型接头。此外,我们发现驱动蛋白重链尾部的相同结构域参与角蛋白和波形蛋白 IF 的运输,这强烈表明多种类型的 IF 沿微管使用相同的机制移动。