Function of the hemochromatosis protein HFE: Lessons from animal models

Figure 2 A model for HFE-me-diated signaling to hepcidin in hepatocytes. A: At low plasma iron concentration, HFE is bound to TfR1 and other proteins involved in signaling to hepcidin remain silent; B: An increase in plasma iron levels results in displacement of HFE from TfR1, followed by iron uptake. This triggers the assembly of a putative “iron-sensing” complex, comprising of HFE, TfR2, BMPs (such as BMP-2, BMP-4 and BMP-9) and their receptor BMPR, and Hjv, which mediates signaling to activate hepcidin transcription via Smad proteins. Thus, the hepatocyte integrates signals for regulation of iron metabolism at the cellular and systemic level.