Binding and uptake of H-ferritin are mediated by human transferrin receptor-1
Binding and uptake of H-ferritin are mediated by human transferrin receptor-1
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DOI：
10.1073/pnas.0913192107
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发表时间：
2010-02-23
影响因子：
11.1
通讯作者：
Seaman, William E.
中科院分区：
文献类型：
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作者：
Li, Li;Fang, Celia J.;Seaman, William E.
铁蛋白是由铁蛋白H链（FHC）和铁蛋白L链（FLC）两种类型的24个亚基组成的球形分子。铁蛋白在细胞内储存铁，但它也循环并与各种细胞类型特异性和饱和结合。对于大多数细胞类型，这种结合可以由仅由FHC组成的铁蛋白介导（HFt），而不能由仅由FLC组成的铁蛋白介导（LFt），这表明铁蛋白与细胞的结合是由FHC介导的，而不是FLC。通过表达克隆，我们发现人类转铁蛋白受体-1 （TfR1）是一个重要的HFt受体，与LFt结合很少或不结合。在体外，HFt可以被可溶性TfR1沉淀，表明这种相互作用不依赖于其他蛋白质。HFt与TfR1的结合被不同的转铁蛋白部分抑制，但HFE几乎没有阻碍，如果有的话。HFt与细胞表面的TfR1结合后，同时进入核内体和溶酶体。在我们研究过的所有细胞系中，HFt与有丝分裂原激活的T细胞和B细胞、循环网状细胞的结合中，TfR1占了大部分（如果不是全部的话）。TfR1可以结合HFt和Tf的证明提出了这种双重受体功能可能通过这些铁结合分子协调铁的加工和使用的可能性。
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.