The chicken yolk sac IgY receptor, a mammalian mannose receptor family member, transcytoses IgY across polarized epithelial cells.
In mammals the transfer of passive immunity from mother to young is mediated by the MHC-related receptor FcRn, which transports maternal IgG across epithelial cell barriers. In birds, maternal IgY in egg yolk is transferred across the yolk sac to passively immunize chicks during gestation and early independent life. The chicken yolk sac IgY receptor (FcRY) is the ortholog of the mammalian phospholipase A2 receptor, a mannose receptor family member, rather than an FcRn or MHC homolog. FcRn and FcRY both exhibit ligand binding at the acidic pH of endosomes and ligand release at the slightly basic pH of blood. Here we show that FcRY expressed in polarized mammalian epithelial cells functioned in endocytosis, bidirectional transcytosis, and recycling of chicken FcY/IgY. Confocal immunofluorescence studies demonstrated that IgY binding and endocytosis occurred at acidic but not basic pH, mimicking pH-dependent uptake of IgG by FcRn. Colocalization studies showed FcRY-mediated internalization via clathrin-coated pits and transport involving early and recycling endosomes. Disruption of microtubules partially inhibited apical-to-basolateral and basolateral-to-apical transcytosis, but not recycling, suggesting the use of different trafficking machinery. Our results represent the first cell biological evidence of functional equivalence between FcRY and FcRn and provide an intriguing example of how evolution can give rise to systems in which similar biological requirements in different species are satisfied utilizing distinct protein folds.
Tesar
Devin B
DB
Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Cheung
Evelyn J
EJ
Bjorkman
Pamela J
PJ
D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D002642:Chick Embryo; D004705:Endocytosis / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D007116:Immunization, Passive; D007136:Immunoglobulins / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D054507:Receptors, Phospholipase A2 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015017:Yolk Sac / Q000276:immunology* / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; C016512:IgY; D007136:Immunoglobulins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; D054507:Receptors, Phospholipase A2; D011994:Recombinant Proteins; C100688:Fc receptor, neonatal