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Harvard, United States

Weflen A.W.,Boston Childrens Hospital | Weflen A.W.,Harvard University | Baier N.,Boston Childrens Hospital | Tang Q.-J.,Boston Childrens Hospital | And 12 more authors.
Molecular Biology of the Cell | Year: 2013

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 endo-somes. 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. © 2013 Weflen et al.

Saslowsky D.E.,Boston Childrens Hospital | Saslowsky D.E.,Harvard Digestive Diseases Center | Saslowsky D.E.,Harvard University | Te Welscher Y.M.,Boston Childrens Hospital | And 10 more authors.
Journal of Biological Chemistry | Year: 2013

Background: Mechanisms for intracellular lipid sorting remain poorly understood. Results: Polarized epithelial cells sort ganglioside GM1, the receptor for cholera toxin, into distinct retrograde and transcytotic pathways, provided that GM1 contains ceramide domains with short or unsaturated fatty acid chains. Conclusion: Sphingolipid sorting depends on ceramide structure, implicating a mechanism for lipid sorting by lipid shape. Significance: The results identify a lipid-sorting pathway across epithelial barriers with clinical applications. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

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