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MBC in Press, published online ahead of print February 6, 2004
Mol. Biol. Cell 10.1091/mbc.E03-11-0832

A more recent version of this article appeared on April 1, 2004
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Submitted on November 20, 2003
Revised on January 5, 2004
Accepted on January 18, 2004

Bi-directional Transepithelial IgG Transport by a Strongly Polarized Basolateral Membrane Fc{gamma}-Receptor

Steven M. Claypool1, Bonny L. Dickinson2, Jessica S. Wagner2, Finn-Eirik Johansen2, Nanda Venu2, Jason A. Borawski2, Wayne I. Lencer3, and Richard S. Blumberg4*

1 Harvard Medical School, Program in Immunology and Departments of Medicine, and Gastroenterology Division, Brigham and Women's Hospital, Boston, MA. 02115
2 Gastrointestinal Cell Biology and Department of Medicine, Children's Hospital, Boston MA. 02115
3 Harvard Medical School, Program in Pediatrics, Brigham and Women's Hospital, Boston, MA. 02115; Gastrointestinal Cell Biology and Department of Medicine, Children's Hospital, Boston MA. 02115; and the Harvard Digestive Diseases Center, Boston, MA. 02115
4 Gastroenterology Division, Brigham and Women's Hospital, Boston, MA. 02115, the Harvard Digestive Diseases Center, Boston, MA. 02115

* Corresponding author. E-mail address: rblumberg{at}partners.org.

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.




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