Transferrin receptor 2: Evidence for ligand-induced stabilization and redirection to a recycling pathway

Martha B. Johnson, Juxing Chen, Nicholas Murchison, Frank A. Green, Caroline Enns

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Abstract

Transferrin receptor 2 (TfR2) is a homologue of transferrin receptor 1 (TfR1), the protein that delivers iron to cells through receptor-mediated endocytosis of diferric transferrin (Fe2Tf). TfR2 also binds Fe 2Tf, but it seems to function primarily in the regulation of systemic iron homeostasis. In contrast to TfR1, the trafficking of TfR2 within the cell has not been extensively characterized. Previously, we showed that Fe 2Tf increases TfR2 stability, suggesting that trafficking of TfR2 may be regulated by interaction with its ligand. In the present study, therefore, we sought to identify the mode of TfR2 degradation, to characterize TfR2 trafficking, and to determine how Fe2Tf stabilizes TfR2. Stabilization of TfR2 by bafilomycin implies that TfR2 traffics to the lysosome for degradation. Confocal microscopy reveals that treatment of cells with Fe2Tf increases the fraction of TfR2 localizing to recycling endosomes and decreases the fraction of TfR2 localizing to late endosomes. Mutational analysis of TfR2 shows that the mutation G679A, which blocks TfR2 binding to Fe2Tf, increases the rate of receptor turnover and prevents stabilization by Fe2Tf, indicating a direct role of Fe 2Tf in TfR2 stabilization. The mutation Y23A in the cytoplasmic domain of TfR2 inhibits its internalization and degradation, implicating YQRV as an endocytic motif.

Original languageEnglish (US)
Pages (from-to)743-754
Number of pages12
JournalMolecular Biology of the Cell
Volume18
Issue number3
DOIs
StatePublished - Mar 2007

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Transferrin Receptors
Ligands
Endosomes
Iron
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Transferrin receptor 2 : Evidence for ligand-induced stabilization and redirection to a recycling pathway. / Johnson, Martha B.; Chen, Juxing; Murchison, Nicholas; Green, Frank A.; Enns, Caroline.

In: Molecular Biology of the Cell, Vol. 18, No. 3, 03.2007, p. 743-754.

Research output: Contribution to journalArticle

Johnson, Martha B. ; Chen, Juxing ; Murchison, Nicholas ; Green, Frank A. ; Enns, Caroline. / Transferrin receptor 2 : Evidence for ligand-induced stabilization and redirection to a recycling pathway. In: Molecular Biology of the Cell. 2007 ; Vol. 18, No. 3. pp. 743-754.
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