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.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Animals
-
Cell Line
-
Cross-Linking Reagents / chemistry
-
Endosomes / metabolism
-
Green Fluorescent Proteins / metabolism
-
Hemagglutinins / metabolism
-
Histocompatibility Antigens Class I / chemistry
-
Histocompatibility Antigens Class I / genetics
-
Histocompatibility Antigens Class I / metabolism*
-
Humans
-
Immunoglobulin G / metabolism
-
Lysosomes / metabolism*
-
Mice
-
Protein Binding
-
Protein Structure, Tertiary
-
Protein Transport
-
Receptors, Fc / chemistry
-
Receptors, Fc / genetics
-
Receptors, Fc / metabolism*
-
Receptors, Polymeric Immunoglobulin / metabolism*
-
Receptors, Transferrin / metabolism
-
Recombinant Fusion Proteins / metabolism
-
beta 2-Microglobulin / metabolism
Substances
-
Cross-Linking Reagents
-
Hemagglutinins
-
Histocompatibility Antigens Class I
-
Immunoglobulin G
-
Receptors, Fc
-
Receptors, Polymeric Immunoglobulin
-
Receptors, Transferrin
-
Recombinant Fusion Proteins
-
beta 2-Microglobulin
-
enhanced green fluorescent protein
-
Green Fluorescent Proteins
-
Fc receptor, neonatal