Focal adhesions are hotspots for keratin filament precursor formation.
Focal adhesions are hotspots for keratin filament precursor formation.
复制标题
焦点粘连是角蛋白细丝前体形成的热点。
DOI：
10.1083/jcb.200511124
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发表时间：
2006-05-08
影响因子：
7.8
通讯作者：
Leube, Rudolf E
中科院分区：
文献类型：
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作者：
Windoffer, Reinhard;Kolsch, Anne;Woll, Stefan;Leube, Rudolf E
最近的研究表明，角蛋白细丝(KF)的形成主要起源于靠近富含肌动蛋白的细胞皮质的部位。为了进一步确定这些部位的特征，我们对活细胞进行了多色荧光成像，发现在肌动蛋白周转率升高的区域，即在片状脂媒中，KF组装急剧增加。在肌动蛋白应激纤维末端的这些区域内出现了丰富的KF前体(KFP)，它们沿着应激纤维移动，直到它们整合到外周KF网络中。最早的KFP是在肌动蛋白锚定的灶性粘连(FAs)旁边被检测到的，只有在新出现的板层粘连(FA)建立之后才能看到。FAs和KFP形成的紧密时空耦合不仅限于上皮细胞，也发生在非上皮细胞和产生突变角蛋白的细胞中。最后，Talin短发夹状RNA干扰FA的形成，导致KFP耗尽。总体而言，我们的结果支持FAs对KF组装的主要调节功能，从而为细胞重新定位和重排过程中整个细胞骨架的协调成形提供了基础。
Recent studies showed that keratin filament (KF) formation originates primarily from sites close to the actin-rich cell cortex. To further characterize these sites, we performed multicolor fluorescence imaging of living cells and found drastically increased KF assembly in regions of elevated actin turnover, i.e., in lamellipodia. Abundant KF precursors (KFPs) appeared within these areas at the distal tips of actin stress fibers, moving alongside the stress fibers until their integration into the peripheral KF network. The earliest KFPs were detected next to actin-anchoring focal adhesions (FAs) and were only seen after the establishment of FAs in emerging lamellipodia. Tight spatiotemporal coupling of FAs and KFP formation were not restricted to epithelial cells, but also occurred in nonepithelial cells and cells producing mutant keratins. Finally, interference with FA formation by talin short hairpin RNA led to KFP depletion. Collectively, our results support a major regulatory function of FAs for KF assembly, thereby providing the basis for coordinated shaping of the entire cytoskeleton during cell relocation and rearrangement.