Defective trafficking and localization of mutated transferrin receptor 2: Implications for type 3 hereditary hemochromatosis

被引:15
作者
Wallace, Daniel F. [1 ]
Summerville, Lesa [1 ]
Crampton, Emily M. [1 ]
Subramaniam, V. Nathan [1 ]
机构
[1] Queensland Inst Med Res, Membrane Transport Lab, Brisbane, Qld 4006, Australia
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2008年 / 294卷 / 02期
关键词
iron overload; aberrant localization; endoplasmic reticulum; mislocalization;
D O I
10.1152/ajpcell.00492.2007
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Transferrin receptor 2 (TfR2), a homologue of transferrin receptor 1 (TfR1), is a key molecule involved in the regulation of iron homeostasis. Mutations in TfR2 result in iron overload with similar features to HFE-associated hereditary hemochromatosis. The precise role of TfR2 in iron metabolism and the functional consequences of disease-causing mutations have not been fully determined. We have expressed wild-type and various mutant forms of TfR2 that are associated with human disease in a mouse liver cell line. Intracellular and surface analysis shows that all the TfR2 mutations analyzed cause the intracellular retention of the protein in the endoplasmic reticulum, whereas the wild-type protein is expressed in endocytic structures and at the cell surface. Our results indicate that the majority of mutations that cause type 3 hereditary hemochromatosis are a consequence of the defective localization of the protein.
引用
收藏
页码:C383 / C390
页数:8
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