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Originally published as MBC in Press, 10.1091/mbc.E03-11-0832 on February 6, 2004

Vol. 15, Issue 4, 1746-1759, April 2004

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

Steven M. Claypool * {dagger}, Bonny L. Dickinson {ddagger}, Jessica S. Wagner {ddagger}, Finn-Eirik Johansen {ddagger}, Nanda Venu {ddagger}, Jason A. Borawski {ddagger}, Wayne I. Lencer {ddagger} ¶ #, and Richard S. Blumberg {dagger} § ¶ #

* 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; {dagger} Harvard Medical School, Department of Gastroenterology Division, Brigham and Women's Hospital, Boston, Massachusetts 02115; {ddagger} 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

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.

Abbreviations used: {beta}2m, {beta}2-microglobulin; h{beta}2m, human {beta}2m; hFcRn, human FcRn; hFcRntl-, tailless hFcRn; IMCD, inner medullary collecting duct; MDCK, Madin-Darby canine kidney; NIP, 5-iodo-4-hydroxy-3-nitro-phenylacetyl; NIP-hIgG1, humanized, NIP-specific human IgG1 monoclonal antibody; pIgR, polymeric immunoglobulin receptor; TfnR, transferrin receptor.

Article published online ahead of print. Mol. Biol. Cell 10.1091/mbc.E03–11–0832. Article and publication date are available at www.molbiolcell.org/cgi/doi/10.1091/mbc.E03–11–0832.

Online version of this article contains supplemental figures. Online version is available at www.molbiolcell.org.

# Corresponding author. Mailing address: Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115. E-mail address: rblumberg{at}partners.org or Gastrointestinal Cell and Developmental Biology, Gastroenterology and Nutrition Division, Children's Hospital, 300 Longwood Ave, Boston, MA 02115. E-mail address: wayne.lencer{at}tch.harvard.edu.




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