TFRC Native

The existence of a receptor for transferrin iron uptake has been recognized since the late 1950s . There are two main types of transferrin receptors in humans: transferrin receptor 1 (TfR1) and transferrin receptor 2 (TfR2) . Both of these receptors are transmembrane glycoproteins, but they differ in their expression patterns and affinity for transferrin.

• TfR1 is a high-affinity receptor that is ubiquitously expressed in various cell types. It is encoded by the TFRC gene and is also known as Cluster of Differentiation 71 (CD71) .
• TfR2 has a lower affinity for transferrin compared to TfR1 and its expression is restricted to certain cell types .

The primary function of the transferrin receptor is to mediate the uptake of iron into cells. This process occurs through receptor-mediated endocytosis, where the transferrin-iron complex binds to the receptor and is internalized into the cell . Once inside the cell, iron is released from transferrin and utilized for various cellular functions.

The production of transferrin receptors is tightly regulated by intracellular iron levels. Low iron concentrations promote increased levels of transferrin receptor to enhance iron intake into the cell . This regulation is mediated by iron-responsive element-binding proteins (IRP1 and IRP2), which bind to the iron-responsive elements (IREs) in the 3’ untranslated region (UTR) of the TfR mRNA . This binding stabilizes the mRNA and prevents its degradation, thereby increasing the production of transferrin receptors.

Transferrin receptors have significant clinical implications. They are often overexpressed in rapidly proliferating cells, such as cancer cells, making them potential targets for cancer therapy . Additionally, mutations in the TFRC gene can lead to various disorders related to iron metabolism.

Recent research has focused on the development of antibody-based therapeutics targeting TfR1 for the treatment of neurological diseases and cancer . For instance, humanized TfR1 knockin mouse models have been developed to assess the efficacy and safety of TfR1-targeted antibody therapies .