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

Wallace, Daniel F., Summerville, Lesa, Crampton, Emily M. and Subramaniam, V. Nathan (2008) Defective trafficking and localization of mutated transferrin receptor 2: Implications for type 3 hereditary hemochromatosis. American Journal of Physiology - Cell Physiology, 294 2: C383-C390. doi:10.1152/ajpcell.00492.2007


Author Wallace, Daniel F.
Summerville, Lesa
Crampton, Emily M.
Subramaniam, V. Nathan
Title Defective trafficking and localization of mutated transferrin receptor 2: Implications for type 3 hereditary hemochromatosis
Journal name American Journal of Physiology - Cell Physiology   Check publisher's open access policy
ISSN 0363-6143
1522-1563
Publication date 2008-02
Sub-type Article (original research)
DOI 10.1152/ajpcell.00492.2007
Volume 294
Issue 2
Start page C383
End page C390
Total pages 8
Place of publication Bethesda, MD, United States
Publisher American Physiological Society
Language eng
Abstract 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.
Keyword iron overload
aberrant localization
endoplasmic reticulum
mislocalization
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Thu, 25 Nov 2010, 10:32:57 EST