Iron Export through the Transporter Ferroportin 1 Is Modulated by the Iron Chaperone PCBP2.
Ferroportin 1 (FPN1) is an iron export protein found in mammals. FPN1 is important for the export of iron across the basolateral membrane of absorptive enterocytes and across the plasma membrane of macrophages. The expression of FPN1 is regulated by hepcidin, which binds to FPN1 and then induces its degradation. Previously, we demonstrated that divalent metal transporter 1 (DMT1) interacts with the intracellular iron chaperone protein poly(rC)-binding protein 2 (PCBP2). Subsequently, PCBP2 receives iron from DMT1 and then disengages from the transporter. In this study, we investigated the function of PCBP2 in iron export. Mammalian genomes encode four PCBPs (i.e. PCBP1-4). Here, for the first time, we demonstrated using both yeast and mammalian cells that PCBP2, but not PCBP1, PCBP3, or PCBP4, binds with FPN1. Importantly, iron-loaded, but not iron-depleted, PCBP2 interacts with FPN1. The PCBP2-binding domain of FPN1 was identified in its C-terminal cytoplasmic region. The silencing of PCBP2 expression suppressed FPN1-dependent iron export from cells. These results suggest that FPN1 exports iron received from the iron chaperone PCBP2. Therefore, it was found that PCBP2 modulates cellular iron export, which is an important physiological process.
From the Department of Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan and.
Izumi
I
Yanatori
the Molecular Pharmacology and Pathology Program, Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia.
Des R
DR
Richardson
From the Department of Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan and.
Kiyoshi
K
Imada
From the Department of Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan and fkishi-ygc@umin.ac.jp.
Fumio
F
Kishi
D001693:Biological Transport, Active / Q000502:physiology; D027682:Cation Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D064451:Hepcidins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D000072417:Protein Domains; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000098742:Ferroportin
D027682:Cation Transport Proteins; D064451:Hepcidins; D018832:Molecular Chaperones; C501903:PCBP2 protein, human; D016601:RNA-Binding Proteins; D000098742:Ferroportin; D007501:Iron
PCBP2; chaperone; ferroportin1; iron; iron metabolism; protein-protein interaction; transporter