Journal
JOURNAL OF CELL BIOLOGY
Volume 185, Issue 4, Pages 673-684Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200809122
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Funding
- National Institutes of Health [RO1 DK53056, RO1 DK48370, DK070856, CA092354]
- Crohns Colitis Foundation
- Harvard Digestive Diseases Center National Institutes of Health [P30 DK034854]
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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.
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