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J. Biol. Chem., Vol. 277, Issue 31, 28038-28050, August 2, 2002
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From the The major histocompatibility complex class
I-related neonatal Fc receptor, FcRn, assembles as a heterodimer
consisting of a heavy chain and
Functional Reconstitution of Human FcRn in Madin-Darby Canine
Kidney Cells Requires Co-expressed Human
2-Microglobulin*
§,
**, and**
Harvard Medical School, Program in
Immunology, and § Gastroenterogy Division, Brigham and
Women's Hospital, the ¶ Gastrointestinal Cell Biology and
Department of Medicine, Children's Hospital, and the Harvard
Digestive Diseases Center, Boston, Massachusetts 02115
2-microglobulin
(2m), which is essential for FcRn function. We observed
that, in Madin-Darby canine kidney (MDCK) cells, the function of human
FcRn in mediating the bidirectional transport of IgG was significantly
increased upon co-expression of the human isoform of 2m.
In MDCK cells, the presence of human 2m endowed upon
human FcRn an enhanced ability to exit the endoplasmic reticulum and
acquire mature carbohydrate side-chain modifications at steady state, a
faster kinetics of maturation, and augmented localization at the cell
surface as a mature glycoprotein able to bind IgG. Although human FcRn
with immature carbohydrate side-chain modifications was capable of
exhibiting pH-dependent binding of IgG, only human FcRn
with mature carbohydrate side-chain modifications was detected on the
cell surface. These results show that human FcRn travels to the cell
surface via the normal secretory pathway and that the appropriate
expression and function of human FcRn in MDCK cells depends upon the
co-expression of human 2m.
*
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.
Supported by NIH Grants DK44319 and DK51362. To whom
correspondence should be addressed: Gastroenterology Division, Dept. of
Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115. Tel.: 617-732-6917; Fax: 617-264-5185; E-mail: rblumberg@partners.org.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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