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Multivalent immune complexes divert FcRn to lysosomes by exclusion from recycling sorting tubules

The neonatal receptor for immunoglobulin G (IgG; FcRn) prevents IgG degradation by efficiently sorting IgG into recycling endosomes and away from lysosomes. When bound to IgG-opsonized antigen complexes, however, FcRn traffics cargo into lysosomes, where antigen processing can occur. Here we address...

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Autores principales: Weflen, Andrew W., Baier, Nina, Tang, Qing-Juan, Van den Hof, Malon, Blumberg, Richard S., Lencer, Wayne I., Massol, Ramiro H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727932/
https://www.ncbi.nlm.nih.gov/pubmed/23741050
http://dx.doi.org/10.1091/mbc.E13-04-0174
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author Weflen, Andrew W.
Baier, Nina
Tang, Qing-Juan
Van den Hof, Malon
Blumberg, Richard S.
Lencer, Wayne I.
Massol, Ramiro H.
author_facet Weflen, Andrew W.
Baier, Nina
Tang, Qing-Juan
Van den Hof, Malon
Blumberg, Richard S.
Lencer, Wayne I.
Massol, Ramiro H.
author_sort Weflen, Andrew W.
collection PubMed
description The neonatal receptor for immunoglobulin G (IgG; FcRn) prevents IgG degradation by efficiently sorting IgG into recycling endosomes and away from lysosomes. When bound to IgG-opsonized antigen complexes, however, FcRn traffics cargo into lysosomes, where antigen processing can occur. Here we address the mechanism of sorting when FcRn is bound to multivalent IgG-opsonized antigens. We find that only the unbound receptor or FcRn bound to monomeric IgG is sorted into recycling tubules emerging from early endosomes. Cross-linked FcRn is never visualized in tubules containing the unbound receptor. Similar results are found for transferrin receptor, suggesting a general mechanism of action. Deletion or replacement of the FcRn cytoplasmic tail does not prevent diversion of trafficking to lysosomes upon cross-linking. Thus physical properties of the lumenal ligand–receptor complex appear to act as key determinants for sorting between the recycling and lysosomal pathways by regulating FcRn entry into recycling tubules.
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spelling pubmed-37279322013-10-16 Multivalent immune complexes divert FcRn to lysosomes by exclusion from recycling sorting tubules Weflen, Andrew W. Baier, Nina Tang, Qing-Juan Van den Hof, Malon Blumberg, Richard S. Lencer, Wayne I. Massol, Ramiro H. Mol Biol Cell Articles The neonatal receptor for immunoglobulin G (IgG; FcRn) prevents IgG degradation by efficiently sorting IgG into recycling endosomes and away from lysosomes. When bound to IgG-opsonized antigen complexes, however, FcRn traffics cargo into lysosomes, where antigen processing can occur. Here we address the mechanism of sorting when FcRn is bound to multivalent IgG-opsonized antigens. We find that only the unbound receptor or FcRn bound to monomeric IgG is sorted into recycling tubules emerging from early endosomes. Cross-linked FcRn is never visualized in tubules containing the unbound receptor. Similar results are found for transferrin receptor, suggesting a general mechanism of action. Deletion or replacement of the FcRn cytoplasmic tail does not prevent diversion of trafficking to lysosomes upon cross-linking. Thus physical properties of the lumenal ligand–receptor complex appear to act as key determinants for sorting between the recycling and lysosomal pathways by regulating FcRn entry into recycling tubules. The American Society for Cell Biology 2013-08-01 /pmc/articles/PMC3727932/ /pubmed/23741050 http://dx.doi.org/10.1091/mbc.E13-04-0174 Text en © 2013 Weflen et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Weflen, Andrew W.
Baier, Nina
Tang, Qing-Juan
Van den Hof, Malon
Blumberg, Richard S.
Lencer, Wayne I.
Massol, Ramiro H.
Multivalent immune complexes divert FcRn to lysosomes by exclusion from recycling sorting tubules
title Multivalent immune complexes divert FcRn to lysosomes by exclusion from recycling sorting tubules
title_full Multivalent immune complexes divert FcRn to lysosomes by exclusion from recycling sorting tubules
title_fullStr Multivalent immune complexes divert FcRn to lysosomes by exclusion from recycling sorting tubules
title_full_unstemmed Multivalent immune complexes divert FcRn to lysosomes by exclusion from recycling sorting tubules
title_short Multivalent immune complexes divert FcRn to lysosomes by exclusion from recycling sorting tubules
title_sort multivalent immune complexes divert fcrn to lysosomes by exclusion from recycling sorting tubules
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727932/
https://www.ncbi.nlm.nih.gov/pubmed/23741050
http://dx.doi.org/10.1091/mbc.E13-04-0174
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