Chaperone protein involved in transmembrane transport of iron.
DMT1 (divalent metal transporter 1) is the main iron importer found in animals, and ferrous iron is taken up by cells via DMT1. Once ferrous iron reaches the cytosol, it is subjected to subcellular distribution and delivered to various sites where iron is required for a variety of biochemical reactions in the cell. Until now, the mechanism connecting the transporter and cytosolic distribution had not been clarified. In the present study, we have identified PCBP2 [poly(rC)-binding protein 2] as a DMT1-binding protein. The N-terminal cytoplasmic region of DMT1 is the binding domain for PCBP2. An interaction between DMT1 and PCBP1, which is known to be a paralogue of PCBP2, could not be demonstrated in vivo or in vitro. Iron uptake and subsequent ferritin expression were suppressed by either DMT1 or PCBP2 knockdown. Iron-associated DMT1 could interact with PCBP2 in vitro, whereas iron-chelated DMT1 could not. These results indicate that ferrous iron imported by DMT1 is transferred directly to PCBP2. Moreover, we demonstrated that PCBP2 could bind to ferroportin, which exports ferrous iron out of the cell. These findings suggest that PCBP2 can transfer ferrous iron from DMT1 to the appropriate intracellular sites or ferroportin and could function as an iron chaperone.
*Department of Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
Izumi
I
Yanatori
*Department of Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
Yumiko
Y
Yasui
*Department of Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
Mitsuaki
M
Tabuchi
*Department of Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.
Fumio
F
Kishi
D027682:Cation Transport Proteins / Q000378:metabolism*; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins; D005296:Ferrous Compounds / Q000378:metabolism; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D005296:Ferrous Compounds; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D007501:Iron; D007502:Iron Chelating Agents; D018832:Molecular Chaperones; D016601:RNA-Binding Proteins; D014168:Transferrin; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C094604:PCBP1 protein, human; C501903:PCBP2 protein, human