Binding and uptake of H-ferritin are mediated by human transferrin receptor-1.
Ferritin is a spherical molecule composed of 24 subunits of two types, ferritin H chain (FHC) and ferritin L chain (FLC). Ferritin stores iron within cells, but it also circulates and binds specifically and saturably to a variety of cell types. For most cell types, this binding can be mediated by ferritin composed only of FHC (HFt) but not by ferritin composed only of FLC (LFt), indicating that binding of ferritin to cells is mediated by FHC but not FLC. By using expression cloning, we identified human transferrin receptor-1 (TfR1) as an important receptor for HFt with little or no binding to LFt. In vitro, HFt can be precipitated by soluble TfR1, showing that this interaction is not dependent on other proteins. Binding of HFt to TfR1 is partially inhibited by diferric transferrin, but it is hindered little, if at all, by HFE. After binding of HFt to TfR1 on the cell surface, HFt enters both endosomes and lysosomes. TfR1 accounts for most, if not all, of the binding of HFt to mitogen-activated T and B cells, circulating reticulocytes, and all cell lines that we have studied. The demonstration that TfR1 can bind HFt as well as Tf raises the possibility that this dual receptor function may coordinate the processing and use of iron by these iron-binding molecules.
Department of Medicine, Veterans Administration Medical Center, San Francisco, CA 94121, USA.
Li
L
Li
Celia J
CJ
Fang
James C
JC
Ryan
Eréne C
EC
Niemi
José A
JA
Lebrón
Pamela J
PJ
Björkman
Hisashi
H
Arase
Frank M
FM
Torti
Suzy V
SV
Torti
Mary C
MC
Nakamura
William E
WE
Seaman
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001052:Apoferritins / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D011485:Protein Binding; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism
D015703:Antigens, CD; C068126:CD71 antigen; D011990:Receptors, Transferrin; D014168:Transferrin; D001052:Apoferritins