Transferrin receptor 2 mediates uptake of transferrin-bound and non-transferrin-bound iron

Ross Graham, G.M. Reutens, C.E. Herbison, R.D. Delima, A.C.G. Chua, John Olynyk, Debbie Trinder

    Research output: Contribution to journalArticle

    33 Citations (Scopus)

    Abstract

    Background/Aims: 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.
    Original languageEnglish
    Pages (from-to)327-334
    JournalJournal of Hepatology
    Volume48
    Issue number2
    DOIs
    Publication statusPublished - 2008

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    Transferrin Receptors
    Transferrin
    Iron
    Cricetulus
    Ovary
    Iron Overload
    Recycling
    Endocytosis
    Radio
    Small Interfering RNA
    Metals

    Cite this

    Graham, Ross ; Reutens, G.M. ; Herbison, C.E. ; Delima, R.D. ; Chua, A.C.G. ; Olynyk, John ; Trinder, Debbie. / Transferrin receptor 2 mediates uptake of transferrin-bound and non-transferrin-bound iron. In: Journal of Hepatology. 2008 ; Vol. 48, No. 2. pp. 327-334.
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    abstract = "Background/Aims: 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.",
    author = "Ross Graham and G.M. Reutens and C.E. Herbison and R.D. Delima and A.C.G. Chua and John Olynyk and Debbie Trinder",
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    Transferrin receptor 2 mediates uptake of transferrin-bound and non-transferrin-bound iron. / Graham, Ross; Reutens, G.M.; Herbison, C.E.; Delima, R.D.; Chua, A.C.G.; Olynyk, John; Trinder, Debbie.

    In: Journal of Hepatology, Vol. 48, No. 2, 2008, p. 327-334.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Transferrin receptor 2 mediates uptake of transferrin-bound and non-transferrin-bound iron

    AU - Graham, Ross

    AU - Reutens, G.M.

    AU - Herbison, C.E.

    AU - Delima, R.D.

    AU - Chua, A.C.G.

    AU - Olynyk, John

    AU - Trinder, Debbie

    PY - 2008

    Y1 - 2008

    N2 - Background/Aims: 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.

    AB - Background/Aims: 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.

    U2 - 10.1016/j.jhep.2007.10.009

    DO - 10.1016/j.jhep.2007.10.009

    M3 - Article

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    SP - 327

    EP - 334

    JO - Journal of Hepatology

    JF - Journal of Hepatology

    SN - 0168-8278

    IS - 2

    ER -