Abstract
Transfer of passive immunity from the mother to the fetus or newborn involves the transport of IgG across several epithelia. Depending on the species, IgG is transported prenatally across the placenta and yolk sac or is absorbed from colostrum and milk by the small intestine of the suckling newborn. In both cases apical to basolateral transepithelial transport of IgG is thought to be mediated by FcRn, an IgG Fc receptor with homology to major histocompatibility class I antigens. Here, we analyzed the intracellular routing of chimera encoding the rat FcRn tail fused to the ecto- and transmembrane domain of the macrophage FcgammaRIIb. Newly synthesized chimera were delivered in a nonvectorial manner to the apical and basolateral cell surface, from where the chimera were able to internalize and transcytose. Apical to basolateral and basolateral to apical transcytosis were differently regulated. This intracellular routing of the chimera is similar to that of the native FcRn, indicating that the cytosolic tail of the receptor is necessary and sufficient to endow an unrelated FcR with the intracellular transport behavior of FcRn. Furthermore, the di-leucine motif in the cytosolic domain of FcRn was required for rapid and efficient endocytosis but not for basolateral sorting of the chimera.
Highlights
Simple epithelia form barriers that allow the selective exchange of molecules between the lumen of an organ and the underlying tissue
Expression of Chimera Encoding Wild-type and Mutant Cytosolic Tails of FcRn (FcRII/FcRn)—To determine the role of the cytosolic tail of FcRn in intracellular transport, we generated chimera in which the ecto- and transmembrane domains of Fc␥RIIb2 were fused to wild-type or mutant cytosolic domains of FcRn (Fig. 1)
Tail-less Fc␥RIIb2 accumulates on the apical surface of MDCK cells because it lacks the cytosolic di-leucine motif required for basolateral sorting and endocytosis [15, 42,43,44], making it an attractive tag to analyze the role of cytosolic tails in targeting to different intracellular compartments or the basolateral plasma membrane [15, 38, 41]
Summary
Simple epithelia form barriers that allow the selective exchange of molecules between the lumen of an organ and the underlying tissue. Fashion to the apical and basolateral cell surface and that they transcytose in both directions.2 To analyze the role of the cytosolic tail in intracellular sorting, we generated MDCK cell lines stably expressing chimera consisting of the ecto- and transmembrane domains of the macrophage Fc␥RIIb and wildtype or mutant cytosolic domains of rFcRn. Newly synthesized FcRII/FcRn receptors were delivered in a nonpolarized manner to the apical and basolateral surface of MDCK cells.
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