Divalent metal transporter 1 : a newly discovered mammalian iron transport protein

Abstract

二价金属离子转运蛋白 1(divalentmetaltransporter 1,DMT1)的发现是近年铁代谢研究领域最重大的一项突破 .DMT1是哺乳类跨膜铁转运蛋白 .这种蛋白质广泛分布于人体各组织 .DMT1mRNA有两种形式 ,一种含有IRE (ironresponseelement) ,而另一种则不含此结构 .DMT1的功能主要是介导小肠上皮细胞的铁吸收以及参与铁从内吞小体移位到胞浆的过程 .DMT1介导的铁转运是一个主动的和H+依赖的过程 .DMT1也参与其他二价金属如Zn2 +、Mn2 +、Co2 +、Cd2 +、Cn2 +、Ni2 +和Pb2 +的转运 .小肠DMT1的表达受饮食或组织铁控制 .第四跨膜区是DMT1的重要功能区 .此区基因发生点突变 (G185R)是导致不可逆性缺铁性贫血的原因 .在帕金森氏病人的黑质发现DMT1表达异常增加 ,因而DMT1可能也与某些神经退行性疾病的形成有关 . The discovery of DMT1 (divalent metal transporter 1, also named as Nramp2 nature resistance associated macrophage protein 2, or DCT1 Divalent cation transporter 1) is the most important breakthrough in the field of mammalian iron metabolism in recent years. It was first identified on the basis of its homology to Nramp1 in 1995. In 1997, two groups independently identified DMT1 as the first mammalian transmembrane iron transporter. Since then, considerable research effort has been devoted to studying this newly discovered protein and the understanding of DMT1 has been greatly imporved. The current knowledge of DMT1 is summarized, including its distribution, structure and different splice forms, expression regulation, physiological function and relationship between the disruption of its expression and the pathogenesis of some diseases. 还原