Transferrin receptor 2 is emerging as a major player in the control of iron metabolism

Abstract

Our knowledge of mammalian iron metabolism has advanced dramatically over recent years. Iron is an essential element for virtually all living organisms. Its intestinal absorption and accurate cellular regulation is strictly required to ensure the coordinated synthesis of the numerous iron-containing proteins involved in key metabolic processes, while avoiding the uptake of excess iron that can lead to organ damage. A range of different proteins exist to ensure this fine control within the various tissues of the body. Among these proteins, transferrin receptor (TFR2) seems to play a key role in the regulation of iron homeostasis. Disabling mutations in TFR2 are responsible for type 3 hereditary hemochromatosis (Type 3 HH). This review describes the biological properties of this membrane receptor, with a particular emphasis paid to the structure, function and cellular localization. Although much information has been garnered on TFR2, further efforts are needed to elucidate its function in the context of the iron regulatory network.

Cross-talk between the mitogen activated protein kinase and bone morphogenetic protein/hemojuvelin pathways is required for the induction of hepcidin by holotransferrin in primary mouse hepatocytes

“…11 We present here the first evidence that the same activation is operating in hepatocytes and that ERK activation is necessary for holotransferrin-induced hepcidin gene expression. Interestingly, we also showed that holotransferrin regulates hepcidin mRNA concentrations through a HJV/BMP dependent pathway since the effect of holotransferrin was lost in the presence of noggin and BMP2/4 antibodies.…”