转铁蛋白受体受到血色素沉着症蛋白HFE的负调控：对细胞铁稳态的影响。
Transferrin receptor is negatively modulated by the hemochromatosis protein HFE: implications for cellular iron homeostasis.
作者信息
Salter-Cid L, Brunmark A, Li Y, Leturcq D, Peterson P A, Jackson M R, Yang Y
机构信息
The R. W. Johnson Pharmaceutical Research Institute, 3535 General Atomics Court, San Diego, CA 92121, USA.
出版信息
Proc Natl Acad Sci U S A. 1999 May 11;96(10):5434-9. doi: 10.1073/pnas.96.10.5434.
Abstract
Hereditary hemochromatosis is a common autosomal recessive disorder of iron metabolism. Recent demonstration of an association between transferrin receptor (TfR) and HFE, a major histocompatibility complex class I-like molecule that has been implicated to play a role in hereditary hemochromatosis, further strengthens the notion that HFE is involved in iron metabolism. Herein we show that TfR is required for and controls the assembly and the intracellular transport and surface expression of HFE. Because surface-expressed HFE and TfR remain firmly associated physically, only the fraction of TfR that is associated with HFE during biosynthesis is affected functionally. Moreover, we show that HFE binding reduces the number of functional transferrin binding sites and impairs TfR internalization, thus reducing the uptake of transferrin-bound iron. Thus, iron homeostasis is indirectly regulated by HFE, a negative modulator of TfR.
摘要
遗传性血色素沉着症是一种常见的常染色体隐性铁代谢紊乱疾病。最近有研究表明转铁蛋白受体（TfR）与HFE之间存在关联，HFE是一种主要组织相容性复合体I类样分子，被认为在遗传性血色素沉着症中发挥作用，这进一步强化了HFE参与铁代谢的观点。在此我们表明，TfR是HFE组装、细胞内运输及表面表达所必需的，并对其具有调控作用。由于表面表达的HFE与TfR在物理上保持紧密结合，因此在生物合成过程中，只有与HFE结合的那部分TfR在功能上受到影响。此外，我们还表明，HFE的结合会减少功能性转铁蛋白结合位点的数量，并损害TfR的内化，从而减少转铁蛋白结合铁的摄取。因此，铁稳态是由HFE间接调节的，HFE是TfR的一种负性调节因子。
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Co-trafficking of HFE, a nonclassical major histocompatibility complex class I protein, with the transferrin receptor implies a role in intracellular iron regulation.遗传性血色素沉着症蛋白（HFE）是一种非经典的主要组织相容性复合体I类蛋白，它与转铁蛋白受体共同转运，这意味着其在细胞内铁调节中发挥作用。
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