HFE association with transferrin receptor 2 increases cellular uptake of transferrin-bound iron.
Mutations in either HFE or transferrin receptor 2 (TfR2) cause decreased expression of the iron regulatory hormone hepcidin and hemochromatosis. HFE and TfR2 were recently discovered to form a stable complex at the cell membrane when co-expressed in heterologous cell lines. We analyzed the functional consequences of the co-expression of these proteins using transfected TRVb cells, a Chinese hamster ovary derived cell line without endogenous HFE or transferrin receptor. The co-expression of TfR2 in TRVb cells expressing HFE led to accelerated HFE biosynthesis and late-Golgi maturation, suggesting interaction prior to cell surface localization. The co-expression of HFE in cells expressing TfR2 led to increased affinity for diferric transferrin, increased transferrin-dependent iron uptake, and relative resistance to iron chelation. These observations indicate that HFE influences the functional properties of TfR2, and suggests a model in which the interaction of these proteins might influence signal transduction to hepcidin.
Waheed
Abdul
A
Edward A. Doisy Department of Biochemistry & Molecular Biology, Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Britton
Robert S
RS
Grubb
Jeffrey H
JH
Sly
William S
WS
Fleming
Robert E
RE
D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis; D006056:Golgi Apparatus / Q000378:metabolism; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; D007501:Iron