Retraction Note to: Binding to the transferrin receptor is required for endocytosis of HFE and regulation of iron homeostasis

Ramalingam, T. S., West, A. P., Lebron, J. A., Nangiana, J. S., Hogan, T. H., Enns, C. A. & Bjorkman, P. J. Binding to the transferrin receptor is required for endocytosis of HFE and regulation of iron homeostasis. Nature Cell Biol.2, 953–957 (2000).

In the course of repeating experiments described in the above paper, we have discovered that some of the confocal microscopy images presented in Figs 1 and 2 were inappropriately processed. A major point of the paper is that wild-type HFE expressed in HuTu-80 cells colocalizes with transferrin receptor (TfR) on the basolateral membrane and in intracellular transferrin (Tf)-positive endosomes, whereas a mutant form of HFE (HFE^W81A) that binds TfR with reduced affinity is localized mainly at the basolateral membrane and not in Tf-positive endosomes. In correctly processed images, we find HFE^W81A both at the basolateral membrane and in Tf-positive vesicles. Although the amount of HFE^W81A at the basolateral membrane versus HFE^W81A in intracellular vesicles is increased when compared with wild-type HFE (N.E. Tiangco and P.J.B., unpublished observations), the differences in HFE localization between cells expressing wild-type HFE and HFE^W81A are subtle. The paper also presents the results of western blots to measure ferritin levels in untransfected cells and cells expressing wild-type HFE, HFE^W81A, the hemochromatosis mutant HFE^C260Y, and wild-type and W81A forms of HFE to which the endosomal sorting sequence from the low-density lipoprotein receptor (LDLR) has been attached. Our current results are in agreement with the findings of the paper: that is, that ferritin levels are lower in HuTu-80 cells expressing wild-type HFE and wild-type HFE–LDLR than in untransfected HuTu-80 cells and in cells expressing HFE^W81A, HFE^W81A–LDLR or HFE^C260Y (A.-S. Zhang and C.A.E., unpublished observations). However, the differences between the present confocal images and the ones published with the paper require us to revise the conclusion that TfR binding by HFE is required for endocytosis of HFE and HFE-mediated regulation of ferritin levels, and we are therefore retracting the paper. We deeply regret any inconvenience this publication has caused for others.

The first author of this paper (T.S.R.) is not a cosignee of this retraction.