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Bidirectional Transepithelial IgG Transport by a Strongly Polarized Basolateral Membrane Fc-Receptor*

Claypool, Steven M., Bonny L. Dickinson , Jessica S. Wagner , Finn-Eirik Johansen , Nanda Venu , Jason A. Borawski , Wayne I. Lencer  and Richard S. Blumberg, 2004, Mol. Biol. Cell 15(4):1746-1759.
* Harvard Medical School, Program in Immunology, Brigham and Women's Hospital, Boston, Massachusetts 02115;   Harvard Medical School, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115;   Harvard Medical School, Department of Gastroenterology Division, Brigham and Women's Hospital, Boston, Massachusetts 02115;   Gastrointestinal Cell Biology and Department of Medicine, Children's Hospital, Boston Massachusetts 02115; and ¶ the Harvard Digestive Diseases Center, Boston, Massachusetts 02115

Submitted November 20, 2003; Revised January 5, 2004; Accepted January 18, 2004
Monitoring Editor: Keith Mostov

Abstract

The human MHC class I–related neonatal Fc receptor, hFcRn, mediates bidirectional transport of IgG across mucosal barriers. Here, we find that at steady state hFcRn distributes predominantly to an apical intracellular compartment and almost exclusively to the basolateral cell surface of polarized epithelial cells. It moves only transiently to the apical membrane. Ligand binding does not redistribute the steady state location of the receptor. Removal of the cytoplasmic tail that contains di-leucine and tryptophan-based endocytosis motifs or incubation at low temperature (18°C) redistributes the receptor apically. The rates of endocytosis of the full-length hFcRn from the apical or basolateral membrane domains, however, are equal. Thus, the strong cell surface polarity displayed by hFcRn results from dominant basolateral sorting by motifs in the cytoplasmic tail that nonetheless allows for a cycle of bidirectional transcytosis.

*Note:   The normal Chicken IgY  used in this publication was produced by Gallus Immunotech Inc.  For more information, please visit our Normal IgY web page or see the Normal IgY product specification sheet.

 
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