Noncanonical Role of Transferrin Receptor 1 is Essential for Intestinal Homeostasis

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2015 Sep 2

PMID 26324903

Citations 51

Authors

Alan C Chen

Adriana Donovan

Renee Ned-Sykes

Nancy C Andrews

Affiliations

Soon will be listed here.

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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