Ferritin forms dynamic oligomers to associate with microtubules in vivo: Implication for the role of microtubules in iron metabolism
Ferritin forms dynamic oligomers to associate with microtubules in vivo: Implication for the role of microtubules in iron metabolism
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DOI：
10.1016/j.yexcr.2006.02.023
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发表时间：
2006-07-01
影响因子：
3.7
通讯作者：
Nakagawa, Hiroyuki
中科院分区：
文献类型：
--
作者：
Hasan, Mohammad Rubayet;Koikawa, Sayaka;Nakagawa, Hiroyuki
铁蛋白是一种普遍分布的铁储存蛋白，据报道在体外与微管相互作用（Hasan 等人，2005，FEBS 杂志 272：822-831）。在这里，我们证明铁蛋白以寡聚形式与微管结合，并且与体外未结合的铁蛋白部分相比，微管结合的铁蛋白含有超过两倍量的铁。间接免疫荧光显微镜显示，在多种细胞系中，很大一部分铁蛋白分子以寡聚物形式与微管共定位。这些发现与显微注射到活人肝癌细胞中的罗丹明标记的铁蛋白的立即寡聚化一致。铁蛋白寡聚体在细胞质中是动态的，抗微管药物显着抑制了它们的细胞内运动。用铁供体柠檬酸铁铵处理细胞显着增加了含有铁蛋白寡聚物的细胞数量。另一方面，当细胞（例如小鼠神经母细胞瘤细胞）缺乏铁时，铁蛋白寡聚体位于微管致密的神经突轴中，但从微管缺陷的神经突尖端消失。这些数据表明微管为富铁铁蛋白的细胞质分布和运输提供了支架，并暗示了微管在铁代谢中的作用。 (c) 2006 Elsevier Inc. 保留所有权利。
Ferritin, a ubiquitously distributed iron storage protein, has been reported to interact with microtubules in vitro (Hasan et al., 2005, FEBS journal 272:822-831). Here, we demonstrate that ferritin binds with the microtubules in an oligomeric form and that the microtubule-bound ferritin contains more than two-fold amount of iron compared to the unbound ferritin fraction in vitro. Indirect immunofluorescence microscopy showed that a significant fraction of the ferritin molecules colocalized with the microtubules as oligomers in a wide variety of cell lines. These findings are consistent with the immediate oligomerization of rhodamine-labeled ferritin, microinjected in living human hepatoma cells. Ferritin oligomers were dynamic in the cytoplasm, and an anti-microtubule drug significantly inhibited their intracellular movement. Treatment of cells with an iron donor, ferric ammonium citrate, remarkably increased the number of cells containing ferritin oligomers. on the other hand, when the cells, such as mouse neuroblastoma cells, were deprived of iron, ferritin oligomers were localized in the microtubule dense, neurite shafts, but were disappeared from the microtubule deficient neurite tips. These data indicate that the microtubules provide a scaffold for the cytoplasmic distribution and transport of the iron-rich ferritin and implicate the role of microtubules in iron metabolism. (c) 2006 Elsevier Inc. All rights reserved.