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

Abstract:

: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.

journal_name

Mol Biol Cell

authors

Weflen AW,Baier N,Tang QJ,Van den Hof M,Blumberg RS,Lencer WI,Massol RH

doi

10.1091/mbc.E13-04-0174

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

2398-405

issue

15

eissn

1059-1524

issn

1939-4586

pii

mbc.E13-04-0174

journal_volume

24

pub_type

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