Silvestri Laura, Nai Antonella, Pagani Alessia, Camaschella Clara
Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Università Vita-Salute San Raffaele Milan, Italy.
Front Pharmacol. 2014 May 7;5:93. doi: 10.3389/fphar.2014.00093. eCollection 2014.
Transferrin receptor 2 (TFR2), a protein homologous to the cell iron importer TFR1, is expressed in the liver and erythroid cells and is reported to bind diferric transferrin, although at lower affinity than TFR1. TFR2 gene is mutated in type 3 hemochromatosis, a disorder characterized by iron overload and inability to upregulate hepcidin in response to iron. Liver TFR2 is considered a sensor of diferric transferrin, possibly in a complex with hemochromatosis protein. In erythroid cells TFR2 is a partner of erythropoietin receptor (EPOR) and stabilizes the receptor on the cell surface. However, Tfr2 null mice as well as TFR2 hemochromatosis patients do not show defective erythropoiesis and tolerate repeated phlebotomy. The iron deficient Tfr2-Tmprss6 double knock out mice have higher red cells count and more severe microcytosis than the liver-specific Tfr2 and Tmprss6 double knock out mice. TFR2 in the bone marrow might be a sensor of iron deficiency that protects against excessive microcytosis in a way that involves EPOR, although the mechanisms remain to be worked out.
转铁蛋白受体2（TFR2）是一种与细胞铁导入蛋白TFR1同源的蛋白质，在肝脏和红细胞中表达，据报道它能结合三价铁转铁蛋白，但其亲和力低于TFR1。TFR2基因在3型血色素沉着症中发生突变，该疾病的特征是铁过载以及无法对铁作出反应而上调铁调素。肝脏中的TFR2被认为是三价铁转铁蛋白的传感器，可能与血色素沉着症蛋白形成复合物。在红细胞中，TFR2是促红细胞生成素受体（EPOR）的伙伴，并使该受体稳定在细胞表面。然而，Tfr2基因敲除小鼠以及TFR2血色素沉着症患者并未表现出红细胞生成缺陷，并且能耐受反复放血。与肝脏特异性Tfr2和Tmprss6双基因敲除小鼠相比，缺铁的Tfr2-Tmprss6双基因敲除小鼠具有更高的红细胞计数和更严重的小红细胞症。骨髓中的TFR2可能是一种缺铁传感器，它以一种涉及EPOR的方式防止过度的小红细胞症，尽管其机制仍有待阐明。
