Comparative analysis of the functional properties of human and mouse ferroportin
- Department of Pharmacology & Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States; Medical Sciences Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States; Systems Biology & Physiology Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States
- Department of Pharmacology & Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States; Systems Biology & Physiology Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States
- Department of Pharmacology & Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States; Department of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
- Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Ferroportin (Fpn)—expressed at the plasma membrane of macrophages, enterocytes, and hepatocytes—mediates the transfer of cellular iron into the blood plasma. Under the control of the iron-regulatory hormone hepcidin, Fpn serves a critical role in systemic iron homeostasis. Although we have previously characterized human Fpn, a great deal of research in iron homeostasis and disorders uses mouse models. By way of example, the flatiron mouse, a model of classical ferroportin disease, bears the mutation H32R in Fpn and is characterized by systemic iron deficiency and macrophage iron retention. The flatiron mouse also appears to exhibit a manganese phenotype, raising the possibility that mouse Fpn serves a role in manganese metabolism. At odds with this observation, we have found that human Fpn does not transport manganese, so we considered the possibility that a species difference could explain this discrepancy. We tested the hypothesis that mouse but not human Fpn can transport manganese and performed a comparative analysis of mouse and human Fpn. We examined the functional properties of human Fpn, mouse Fpn, and mutant mouse Fpn by using radiotracer assays in RNA-injected Xenopus oocytes. We found that neither mouse nor human Fpn transports manganese. Mouse and human Fpn share identical properties with respect to substrate profile, calcium dependence, optimal pH, and hepcidin sensitivity. We have also demonstrated that Fpn is not an ATPase pump. Our findings validate the use of mouse models of ferroportin function in iron homeostasis and disease.
- Research Organization:
- US Department of Energy (USDOE), Washington, DC (United States). Office of Science, Nuclear Physics (NP)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 2424952
- Journal Information:
- American Journal of Physiology: Cell Physiology, Journal Name: American Journal of Physiology: Cell Physiology Journal Issue: 5 Vol. 324; ISSN 0363-6143
- Publisher:
- American Physiological Society
- Country of Publication:
- United States
- Language:
- English
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