title: Transferrin receptor 2 mediates uptake of transferrin-bound and non-transferrin-bound iron.
abstract: OBJECTIVE
  Transferrin receptor 2 appears to have dual roles in iron metabolism; one is signalling, the other is iron transport. It is sensitive to high levels of diferric transferrin, which is associated with disorders of iron overload. Also present in these disorders are increased levels of plasma non-transferrin-bound iron. This study sought to clarify the role of transferrin receptor 2 in the uptake of transferrin-bound and non-transferrin-bound iron.
  
  
  METHODS
  Variant Chinese Hamster Ovary (CHO) cells, transfected with transferrin receptor 2, were incubated with radio-labelled transferrin-bound or non-transferrin-bound iron. Competition studies were performed in the presence of unlabelled dimetallic transferrin; knockdown was performed using specific siRNA.
  
  
  RESULTS
  Cells expressing transferrin receptor 2 bound and internalised transferrin and transferrin-bound iron. Transferrin recycling occurred with an average cycling time of 11-15 min. Interestingly, the presence of transferrin receptor 2 was also associated with uptake of non-transferrin-bound iron which was inhibited by unlabelled transferrin-bound metals. Knockdown reduced transferrin-bound and non-transferrin-bound iron uptake by approximately 60%.
  
  
  CONCLUSIONS
  Transferrin receptor 2 mediates transferrin-bound iron uptake by receptor-mediated endocytosis. It is also involved in the uptake of non-transferrin-bound iron and the inhibition of non-transferrin-bound iron uptake by diferric transferrin in CHO cells.
authors: School of Medicine and Pharmacology, The University of Western Australia, Fremantle Hospital, P.O. Box 480, Fremantle, WA 6959, Australia. rmgraham@meddent.uwa.edu.au
authors: Ross M
authors: RM
authors: Graham
authors: Gail M
authors: GM
authors: Reutens
authors: Carly E
authors: CE
authors: Herbison
authors: Roheeth D
authors: RD
authors: Delima
authors: Anita C G
authors: AC
authors: Chua
authors: John K
authors: JK
authors: Olynyk
authors: Debbie
authors: D
authors: Trinder
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007501:Iron / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D011990:Receptors, Transferrin / Q000502:physiology*; D014168:Transferrin / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D014168:Transferrin; D007501:Iron