The keratin-filament cycle of assembly and disassembly

The keratin-filament cycle of assembly and disassembly
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DOI:
10.1242/jcs.068080
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发表时间:
2010-07-01
影响因子:
4
通讯作者:
Leube, Rudolf E.
Leube, Rudolf E.
中科院分区:
生物学2区
文献类型:
--
作者:
Koelsch, Anne;Windoffer, Reinhard;Leube, Rudolf E.

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细胞骨架的连续和受调控的重塑对于许多基本细胞功能至关重要。与肌动蛋白丝和微管相比,尚不清楚第三种主要细胞骨架丝系统(由中间丝多肽组成)是如何实现这一点的。使用活体间期细胞的延时荧光显微镜,结合光漂白、光活化和定量荧光测量,我们观察到上皮角蛋白中间丝不断释放非丝状亚基,这些亚基在细胞外周重新用于丝状组装。该循环与蛋白质生物合成无关。循环的不同阶段发生在确定的细胞亚域中:组装发生在细胞外围,新形成的细丝不断地被运送到核周区域,同时发生分解,产生可扩散的亚基,用于另一轮外围组装。剩余的核旁丝稳定并包裹着细胞核。我们的数据表明,角蛋白丝​​的组装和分解循环是中间丝网络可塑性的主要机制,可以快速适应特定的要求,特别是在迁移细胞中。
Continuous and regulated remodelling of the cytoskeleton is crucial for many basic cell functions. In contrast to actin filaments and microtubules, it is not understood how this is accomplished for the third major cytoskeletal filament system, which consists of intermediate-filament polypeptides. Using time-lapse fluorescence microscopy of living interphase cells, in combination with photobleaching, photoactivation and quantitative fluorescence measurements, we observed that epithelial keratin intermediate filaments constantly release non-filamentous subunits, which are reused in the cell periphery for filament assembly. This cycle is independent of protein biosynthesis. The different stages of the cycle occur in defined cellular subdomains: assembly takes place in the cell periphery and newly formed filaments are constantly transported toward the perinuclear region while disassembly occurs, giving rise to diffusible subunits for another round of peripheral assembly. Remaining juxtanuclear filaments stabilize and encage the nucleus. Our data suggest that the keratin-filament cycle of assembly and disassembly is a major mechanism of intermediate-filament network plasticity, allowing rapid adaptation to specific requirements, notably in migrating cells.