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Published online
doi:10.1083/jcb.200809122
The Journal of Cell Biology, Vol. 185, No. 4, 673-684
The Rockefeller University Press, 0021-9525 $30.00
© Tzaban et al.
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Article

The recycling and transcytotic pathways for IgG transport by FcRn are distinct and display an inherent polarity



Salit Tzaban1, Ramiro H. Massol1, Elizabeth Yen1, Wendy Hamman1, Scott R. Frank1, Lynne A. Lapierre4,5, Steen H. Hansen1, James R. Goldenring4,5, Richard S. Blumberg2,3, and Wayne I. Lencer1,3

1 Children's Hospital, Gastroenterology Division; 2 Brigham and Women's Hospital, Gastroenterology Division; and the 3 Harvard Digestive Diseases Center, Harvard Medical School, Boston, MA 02115
4 Deptartment of Surgery, Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, TN 37232
5 Nashville Veterans Affairs Medical Center, Nashville, TN 37232

Correspondence to Wayne I. Lencer: wayne.lencer{at}childrens.harvard.edu

The Fc receptor FcRn traffics immunoglobulin G (IgG) in both directions across polarized epithelial cells that line mucosal surfaces, contributing to host defense. We show that FcRn traffics IgG from either apical or basolateral membranes into the recycling endosome (RE), after which the actin motor myosin Vb and the GTPase Rab25 regulate a sorting step that specifies transcytosis without affecting recycling. Another regulatory component of the RE, Rab11a, is dispensable for transcytosis, but regulates recycling to the basolateral membrane only. None of these proteins affect FcRn trafficking away from lysosomes. Thus, FcRn transcytotic and recycling sorting steps are distinct. These results are consistent with a single structurally and functionally heterogeneous RE compartment that traffics FcRn to both cell surfaces while discriminating between recycling and transcytosis pathways polarized in their direction of transport.

Abbreviations used in this paper: ANOVA, analysis of variance; ARE, apical recycling endosome; dIgA, dimeric IgA; MyoVb, myosin Vb; NIP, 4-hydroxy-3-iodo-5-nitrophenylacetyl; pIgR, polymeric Ig receptor; RE, recycling endosome; shRNA, small hairpin RNA; TetR, tetracycline repressor; Tf, transferrin; Tf-R, Tf receptor.

© 2009 Tzaban et al.
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