1. Transferrin receptor 1 is a cellular receptor for human heme-albumin
- Author
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Raif S. Geha, Janet Chou, Hannes Stockinger, Verena Berg, Maria Seyerl-Jiresch, Akihiro Yachie, Alexander Puck, Peter Steinberger, Gerhard J. Zlabinger, Hyeryun Choe, Sarojinidevi Künig, Madhura Modak, Markus Kraller, Brell Jennifer, Leopold Öhler, and Johannes Stöckl
- Subjects
0301 basic medicine ,Cell type ,Cell biology ,Molecular biology ,Iron ,Medicine (miscellaneous) ,Transferrin receptor ,Endocytosis ,General Biochemistry, Genetics and Molecular Biology ,Article ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Antigens, CD ,Albumins ,Receptors, Transferrin ,Humans ,Scavenger receptor ,Heme ,lcsh:QH301-705.5 ,Cell Proliferation ,chemistry.chemical_classification ,Biological Transport ,Ligand (biochemistry) ,Culture Media ,030104 developmental biology ,chemistry ,Gene Expression Regulation ,lcsh:Biology (General) ,Transferrin ,030220 oncology & carcinogenesis ,General Agricultural and Biological Sciences ,Intracellular ,Heme Oxygenase-1 - Abstract
Iron is essential for living cells. Uptake of iron-loaded transferrin by the transferrin receptor 1 (CD71, TFR) is a major but not sufficient mechanism and an alternative iron-loaded ligand for CD71 has been assumed. Here, we demonstrate that CD71 utilizes heme-albumin as cargo to transport iron into human cells. Binding and endocytosis of heme-albumin via CD71 was sufficient to promote proliferation of various cell types in the absence of transferrin. Growth and differentiation of cells induced by heme-albumin was dependent on heme-oxygenase 1 (HO-1) function and was accompanied with an increase of the intracellular labile iron pool (LIP). Import of heme-albumin via CD71 was further found to contribute to the efficacy of albumin-based drugs such as the chemotherapeutic Abraxane. Thus, heme-albumin/CD71 interaction is a novel route to transport nutrients or drugs into cells and adds to the emerging function of CD71 as a scavenger receptor., Brell, Berg et al find that iron enters cells not only through iron-transferrin uptake by the transferrin receptor (CD71) but also through uptake of heme-albumin by this receptor and that heme-albumin stimulates proliferation in a manner dependent on heme oxygenase 1. This study presents a new route for iron uptake in mammalian cells.
- Published
- 2020