TY - JOUR
T1 - Transferrin receptor 2
T2 - Evidence for ligand-induced stabilization and redirection to a recycling pathway
AU - Johnson, Martha B.
AU - Chen, Juxing
AU - Murchison, Nicholas
AU - Green, Frank A.
AU - Enns, Caroline A.
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
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U2 - 10.1091/mbc.E06-09-0798
DO - 10.1091/mbc.E06-09-0798
M3 - Article
C2 - 17182845
AN - SCOPUS:33947111426
SN - 1059-1524
VL - 18
SP - 743
EP - 754
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 3
ER -