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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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