beta(2)-Microglobulin is important for cell surface expression and pH-dependent IgG binding of human FcRn.
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.
Praetor
Asja
A
Institute of Molecular and Cell Biology, Epithelial Cell Biology Laboratory, 30 Medical Drive, Singapore 117609, Republic of Singapore.
Hunziker
Walter
W
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000954:Antigens, Surface / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D005057:Eukaryotic Cells / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011961:Receptors, Fc / Q000276:immunology* / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D011961:Receptors, Fc; D001613:beta 2-Microglobulin; C034241:ribophorin; C100688:Fc receptor, neonatal