Nonvectorial Surface Transport, Endocytosis via a Di-leucine-based Motif, and Bidirectional Transcytosis of Chimera Encoding the Cytosolic Tail of Rat FcRn Expressed in Madin-Darby Canine Kidney Cells*
- From the Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, 155 Ch. des Boveresses, 1066 Epalinges, Switzerland
Abstract
Transfer of passive immunity from the mother to the fetus or newborn involves the transport of IgG across several epithelia. Depending on the species, IgG is transported prenatally across the placenta and yolk sac or is absorbed from colostrum and milk by the small intestine of the suckling newborn. In both cases apical to basolateral transepithelial transport of IgG is thought to be mediated by FcRn, an IgG Fc receptor with homology to major histocompatibility class I antigens. Here, we analyzed the intracellular routing of chimera encoding the rat FcRn tail fused to the ecto- and transmembrane domain of the macrophage FcγRIIb. Newly synthesized chimera were delivered in a nonvectorial manner to the apical and basolateral cell surface, from where the chimera were able to internalize and transcytose. Apical to basolateral and basolateral to apical transcytosis were differently regulated. This intracellular routing of the chimera is similar to that of the native FcRn, indicating that the cytosolic tail of the receptor is necessary and sufficient to endow an unrelated FcR with the intracellular transport behavior of FcRn. Furthermore, the di-leucine motif in the cytosolic domain of FcRn was required for rapid and efficient endocytosis but not for basolateral sorting of the chimera.
Footnotes
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↵* This work was funded by a grant and a career development award from the Swiss National Science Foundation (to W. H.) and supported by the Canton de Vaud.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ Supported in part by the Austrian Science Research Fund (P-12084Med). Present address: Allgemeines Kraukenhaus, Dept. of General and Experimental Pathology, University of Vienna, Vienna, Austria 1090.
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↵§ To whom correspondence should be addressed. Tel.: 41-21-692-5737; Fax: 41-21-692-5705; E-mail: Walter.Hunziker{at}ib.unil.ch.
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↵2 A. Praetor, I. Stefaner, and W. Hunziker, manuscript in preparation.
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↵3 I. Stefaner and W. Hunziker, unpublished observation.
- Abbreviations:
- pIgR
-
polymeric immunoglobulin receptor
- BFA
-
brefeldin A
- CaM
-
calmodulin
- FcR
-
Fc receptor
- FcRn
-
neonatal IgG FcR
- rFcRn
-
rat FcRn
- FcRII/FcRn
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chimera between FcγRIIb2 ecto- and transmembrane domain and FcRn cytosolic tail
- CKII
-
casein kinase II
- MDCK
-
Madin-Darby canine kidney
- PCR
-
polymerase chain reaction
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- Received November 5, 1998.
- Revision received January 11, 1999.
- The American Society for Biochemistry and Molecular Biology, Inc.
