Fetal capillary

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Chorionic villus
Fetal capillary
Intervillous space
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Chorionic villus
Fetal capillary
Intervillous space
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Cytotrophoblast
Syncytiotrophoblast
Endothelial cell
Fetal blood
Stroma
Mothers blood
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How do antibodies cross cells?
IgG
degradation
transport
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Fc
out
in
FcRncyt
FcRn can bind antibodies at the cell surface
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FcRncyt
FcRn enters cell in a membrane vesicle
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Dependence of transport on endosome targeting
signals in IMCD model
Wu Simister 2001
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Tyrosine (and tryptophan) endocytosis signals
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GST pull-down assay for interaction with µ2
µ2
?
FcRncyt
GSH
GST
(His)6
Western Coomassie
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GST pull-down assay for interaction with µ2
mutants
inhibitors
µ2
?
FcRncyt
GSH
GST
(His)6
mutants
Western Coomassie
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FcRn tail pulls down µ2
GST-FcRncytW311A
GST-FcRncyt
Input
GST
Wernick, Haucke Simister 05
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Tyrosine signal competes for µ2
none
WLSL
ALSL
YRAL
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Tyrphostins are tyrosine analogs
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Blocking µ2 binding site inhibits pull down
DMSO
A23
A51
DMSO
A23
A51
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Blocking µ2 binding site inhibits endocytosis
Wernick, Haucke Simister 05
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Summary FcRn binds adaptor protein µ2
Binding depends on Trp-311 Binding depends on
Tyr-binding site of µ2 Endocytosis depends
on Tyr/Trp-binding site of µ2
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Thanks
Free University Berlin Volker Haucke
Brandeis UniversityZhen Wu Naomi
WernickNICHD 27691