Transferrin receptor 2 mediates uptake of transferrin-bound and non-transferrin-bound iron.
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.
Graham
Ross M
RM
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
Reutens
Gail M
GM
Herbison
Carly E
CE
Delima
Roheeth D
RD
Chua
Anita C G
AC
Olynyk
John K
JK
Trinder
Debbie
D
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*
D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D014168:Transferrin; D007501:Iron