Noncanonical role of transferrin receptor 1 is essential for intestinal homeostasis

Proceedings of the National Academy of Sciences of the United States of America
Alan C ChenNancy C Andrews

Abstract

Transferrin receptor 1 (Tfr1) facilitates cellular iron uptake through receptor-mediated endocytosis of iron-loaded transferrin. It is expressed in the intestinal epithelium but not involved in dietary iron absorption. To investigate its role, we inactivated the Tfr1 gene selectively in murine intestinal epithelial cells. The mutant mice had severe disruption of the epithelial barrier and early death. There was impaired proliferation of intestinal epithelial cell progenitors, aberrant lipid handling, increased mRNA expression of stem cell markers, and striking induction of many genes associated with epithelial-to-mesenchymal transition. Administration of parenteral iron did not improve the phenotype. Surprisingly, however, enforced expression of a mutant allele of Tfr1 that is unable to serve as a receptor for iron-loaded transferrin appeared to fully rescue most animals. Our results implicate Tfr1 in homeostatic maintenance of the intestinal epithelium, acting through a role that is independent of its iron-uptake function.

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Citations

Mar 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Pavle MatakNancy C Andrews
Feb 13, 2016·EBioMedicine·Jerry Kaplan, Diane M Ward
Mar 18, 2016·Proceedings of the National Academy of Sciences of the United States of America·Yvette Y Yien, Barry H Paw
Oct 13, 2015·Cell Reports·Wenjing XuNancy C Andrews
May 11, 2016·International Journal of Laboratory Hematology·C CamaschellaL Silvestri
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May 10, 2017·IUBMB Life·Stefania RecalcatiGaetano Cairo
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