title: Defective trafficking and localization of mutated transferrin receptor 2: implications for type 3 hereditary hemochromatosis.
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.
authors: Membrane Transport Laboratory, The Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane, QLD 4006, Australia.
authors: Daniel F
authors: DF
authors: Wallace
authors: Lesa
authors: L
authors: Summerville
authors: Emily M
authors: EM
authors: Crampton
authors: V Nathan
authors: VN
authors: Subramaniam
mesh_terms: D000818:Animals; D002451:Cell Compartmentation / Q000235:genetics; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006432:Hemochromatosis / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D022781:Hepatocytes / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007501:Iron / Q000378:metabolism*; D051379:Mice; D009154:Mutation / Q000235:genetics*; D021381:Protein Transport / Q000235:genetics; D011990:Receptors, Transferrin / Q000235:genetics* / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D011990:Receptors, Transferrin; C503641:TFR2 protein, mouse; D014168:Transferrin; D007501:Iron