N-glycan moieties in neonatal Fc receptor determine steady-state membrane distribution and directional transport of IgG

Timothy T. Kuo, Eric J. de Muinck, Steven M Claypool, Masaru Yoshida, Takashi Nagaishi, Victoria G. Aveson, Wayne I. Lencer, Richard S. Blumberg

Research output: Contribution to journalArticle

Abstract

The neonatal Fc receptor (FcRn) is a major histocompatibility complex class I-related molecule known to protect IgG and albumin from catabolism and transport IgG across polarized epithelial cells in a bidirectional manner. Previous studies have shown species-specific differences in ligand binding, IgG transport direction, and steady-state membrane distribution when expressed in polarized epithelial cells. We hypothesized that these differences may be due to the additional N-glycans expressed on the rat FcRn, because N-glycans have been proposed to function as apical targeting signals, and that two of the N-glycan moieties have been shown to contribute to the IgG binding of rat FcRn. A panel of mutant human FcRn variants was generated to resemble the N-glycan expression of rat FcRn in various combinations and subsequently transfected into Madin-Darby canine kidney II cells together with human β2-microglobulin. Mutant human FcRn clones that contained additional N-glycan side-chain modifications, including that which was fully rodentized, still exhibited specificity for human IgG and failed to bind to mouse IgG. At steady state, the mutant human FcRn with additional N-glycans redistributed to the apical cell surface similar to that of rat FcRn. Furthermore, the rodentized human FcRn exhibited a reversal of IgG transport with predominant transcytosis from an apical-to-basolateral direction, which resembled that of the rat FcRn isoform. These studies show that theN-glycans in FcRn contribute significantly to the steady-state membrane distribution and direction of IgG transport in polarized epithelia.

Original languageEnglish (US)
Pages (from-to)8292-8300
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number13
DOIs
StatePublished - Mar 27 2009
Externally publishedYes

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Polysaccharides
Immunoglobulin G
Membranes
Rats
Epithelial Cells
Transcytosis
Madin Darby Canine Kidney Cells
neonatal Fc receptors
Major Histocompatibility Complex
Albumins
Protein Isoforms
Epithelium
Clone Cells
Ligands
Molecules
Direction compound

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

N-glycan moieties in neonatal Fc receptor determine steady-state membrane distribution and directional transport of IgG. / Kuo, Timothy T.; de Muinck, Eric J.; Claypool, Steven M; Yoshida, Masaru; Nagaishi, Takashi; Aveson, Victoria G.; Lencer, Wayne I.; Blumberg, Richard S.

In: Journal of Biological Chemistry, Vol. 284, No. 13, 27.03.2009, p. 8292-8300.

Research output: Contribution to journalArticle

Kuo, Timothy T. ; de Muinck, Eric J. ; Claypool, Steven M ; Yoshida, Masaru ; Nagaishi, Takashi ; Aveson, Victoria G. ; Lencer, Wayne I. ; Blumberg, Richard S. / N-glycan moieties in neonatal Fc receptor determine steady-state membrane distribution and directional transport of IgG. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 13. pp. 8292-8300.
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