beta(2)-Microglobulin is important for cell surface expression and pH-dependent IgG binding of human FcRn.
Praetor, A; Hunziker, W
Journal of cell science
115
2389-97
2002
Show Abstract
FcRn is a heterodimer of an alpha-chain and beta(2)-microglobulin (beta(2)m) and differs from other IgG Fc receptors in that it is structurally related to MHC class I molecules. Several functions attributed to FcRn are affected in beta(2)-microglobulin (beta(2)m)-deficient mice, suggesting that the alpha-chain needs to assemble with beta(2)m to form a functional receptor. However, the precise role of beta(2)m in FcRn function is not known. Here we expressed the human FcRn alpha-chain alone or in combination with beta(2)m in human melanoma FO-1 cells. We show that beta(2)m is important for cell surface expression of FcRn and that, in the absence of beta(2)m, the receptor is retained in the endoplasmic reticulum. Furthermore, in the absence of beta(2)m, IgG binding is decreased compared with that of native FcRn. Thus, assembly of the FcRn alpha-chain with beta(2)m is important for both transport of FcRn from the ER to the cell surface and efficient pH-dependent IgG binding. | 12006623
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Intracellular traffic of the MHC class I-like IgG Fc receptor, FcRn, expressed in epithelial MDCK cells.
Praetor, A; Ellinger, I; Hunziker, W
Journal of cell science
112 ( Pt 14)
2291-9
1999
Show Abstract
Transfer of passive immunity from 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 MHC class I antigens. We have now expressed the human FcRn in polarized MDCK cells and analyzed the intracellular routing of the receptor. FcRn showed a predominant intracellular localization at steady state. Newly synthesized FcRn was delivered in a non-vectorial fashion to both the apical and basolateral surfaces of MDCK cell monolayers. Following internalization from the apical or basolateral domain, the receptor transcytosed to the opposite surface. These findings provide direct evidence for the transepithelial transport function of FcRn and indicate that the receptor undergoes multiple rounds of transcytosis. | 10381385
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