Chaperone protein involved in transmembrane transport of iron.
Chaperone protein involved in transmembrane transport of iron.
复制标题
DOI：
10.1042/bj20140225
复制
发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
I. Yanatori;Y. Yasui;M. Tabuchi;F. Kishi
中科院分区：
文献类型：
--
作者：
I. Yanatori;Y. Yasui;M. Tabuchi;F. Kishi
DMT1(二价金属转运体1)是动物体内发现的主要铁进口体，细胞通过DMT1摄取亚铁。一旦亚铁到达细胞质，它就会被亚细胞分布，并被输送到细胞内各种生化反应所需的铁的不同部位。到目前为止，转运蛋白和胞浆分布的联系机制还不是很清楚。在本研究中，我们鉴定了PCBP2[聚(RC)结合蛋白2]是一种DMT1结合蛋白。DMT1的N-末端胞质区域是PCBP2的结合域。DMT1和PCBP1之间的相互作用是已知的PCBP2的类似物，在体内和体外都不能证明。铁摄取和随后的铁蛋白表达被DMT1或PCBP2基因敲除所抑制。铁结合的DMT1在体外可以与PCBP2相互作用，而铁螯合的DMT1不能。这些结果表明，DMT1进口的亚铁直接转移到PCBP2。此外，我们还证明了PCBP2可以与铁蛋白结合，铁蛋白可以将亚铁从细胞中排出。这些发现表明，PCBP2可以将亚铁从DMT1转移到适当的细胞内位置或铁孔蛋白，并可能作为铁伴侣发挥作用。
DMT1 (divalent metal transporter 1) is the main iron importer found in animals, and ferrous iron is taken up by cells via DMT1. Once ferrous iron reaches the cytosol, it is subjected to subcellular distribution and delivered to various sites where iron is required for a variety of biochemical reactions in the cell. Until now, the mechanism connecting the transporter and cytosolic distribution had not been clarified. In the present study, we have identified PCBP2 [poly(rC)-binding protein 2] as a DMT1-binding protein. The N-terminal cytoplasmic region of DMT1 is the binding domain for PCBP2. An interaction between DMT1 and PCBP1, which is known to be a paralogue of PCBP2, could not be demonstrated in vivo or in vitro. Iron uptake and subsequent ferritin expression were suppressed by either DMT1 or PCBP2 knockdown. Iron-associated DMT1 could interact with PCBP2 in vitro, whereas iron-chelated DMT1 could not. These results indicate that ferrous iron imported by DMT1 is transferred directly to PCBP2. Moreover, we demonstrated that PCBP2 could bind to ferroportin, which exports ferrous iron out of the cell. These findings suggest that PCBP2 can transfer ferrous iron from DMT1 to the appropriate intracellular sites or ferroportin and could function as an iron chaperone.