Binding and uptake of H-ferritin are mediated by human transferrin receptor-1

被引：462

作者：

Li, Li ^{[1
]}

Fang, Celia J. ^{[1
,2
]}

Ryan, James C. ^{[1
,2
]}

Niemi, Erene C. ^{[2
]}

Lebron, Jose A. ^{[3
]}

Bjorkman, Pamela J. ^{[3
,4
]}

Arase, Hisashi ^{[5
,6
]}

Torti, Frank M. ^{[7
]}

Torti, Suzy V. ^{[8
]}

Nakamura, Mary C. ^{[1
,2
]}

Seaman, William E. ^{[1
,2
,9
]}

机构：

[1] Vet Adm Med Ctr, Dept Med, San Francisco, CA 94121 USA

[2] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[3] CALTECH, Div Biol, Pasadena, CA 91125 USA

[4] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA

[5] Osaka Univ, Dept Immunochem, World Premier Int Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan

[6] Osaka Univ, Microbial Dis Res Inst, Suita, Osaka 5650871, Japan

[7] Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Ctr Comprehens Canc, Winston Salem, NC 27157 USA

[8] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Ctr Comprehens Canc, Winston Salem, NC 27157 USA

[9] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 08期

基金：

美国国家卫生研究院;

关键词：

ferritin; HFE; iron; receptors; endocytosis; HUMAN ERYTHROID PRECURSORS; IRON UPTAKE; EXTRACELLULAR FERRITIN; HEAVY-CHAIN; HUMAN-LIVER; CELLS; EXPRESSION; PROTEIN; STORAGE; FERRIREDUCTASE;

D O I：

10.1073/pnas.0913192107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：3505 / 3510

页数：6

共 43 条

[11] Ferritin uptake by human erythroid precursors is a regulated iron uptake pathway [J].