Visualizing the site and dynamics of IgG salvage by the MHC class I-related receptor, FcRn.
The MHC class I-related receptor, FcRn, plays a central role in regulating the serum levels of IgG. FcRn is expressed in endothelial cells, suggesting that these cells may be involved in maintaining IgG levels. We have used live cell imaging of FcRn-green fluorescent protein transfected human endothelial cells to analyze the intracellular events that control IgG homeostasis. We show that segregation of FcRn-IgG complexes from unbound IgG occurs in the sorting endosome. FcRn or FcRn-IgG complexes are gradually depleted from sorting endosomes to ultimately generate multivesicular bodies whose contents are destined for lysosomal degradation. In addition, the pathways taken by FcRn and the transferrin receptor overlap, despite distinct mechanisms of ligand uptake. The studies provide a dynamic view of the trafficking of FcRn and its ligand and have relevance to understanding how FcRn functions to maintain IgG homeostasis.
Ober
Raimund J
RJ
Cancer Immunobiology Center and Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Martinez
Cruz
C
Vaccaro
Carlos
C
Zhou
Jinchun
J
Ward
E Sally
ES
D001666:Binding Sites, Antibody / Q000235:genetics; D002460:Cell Line; D022162:Cytoplasmic Vesicles / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011992:Endosomes / Q000276:immunology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D049452:Green Fluorescent Proteins; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D018715:Microscopy, Video / Q000379:methods; D008870:Microtubules / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D011961:Receptors, Fc / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011990:Receptors, Transferrin / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection
D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D008024:Ligands; D008164:Luminescent Proteins; D011961:Receptors, Fc; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; C100688:Fc receptor, neonatal