AUTHOR=Silvestri Laura , Nai Antonella , Pagani Alessia , Camaschella Clara 

TITLE=The extrahepatic role of TFR2 in iron homeostasis

JOURNAL=Frontiers in Pharmacology

VOLUME=5

YEAR=2014

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2014.00093

DOI=10.3389/fphar.2014.00093

ISSN=1663-9812

ABSTRACT=<p>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. <italic>TFR2</italic> 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, <italic>Tfr2</italic> null mice as well as <italic>TFR2</italic> hemochromatosis patients do not show defective erythropoiesis and tolerate repeated phlebotomy. The iron deficient <italic>Tfr2-Tmprss6</italic> double knock out mice have higher red cells count and more severe microcytosis than the liver-specific <italic>Tfr2</italic> and <italic>Tmprss6</italic> 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.</p>