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Fcgrt  -  Fc fragment of IgG, receptor, transporter,...

Rattus norvegicus

Synonyms: FcRn, Fcrn, IgG Fc fragment receptor transporter alpha chain, IgG receptor FcRn large subunit p51, Neonatal Fc receptor
 
 
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Disease relevance of Fcgrt

  • Hypoalbuminemia was also examined in two strains of FcRn-deficient mice: beta(2)-microglobulin (beta(2)M) knockout (KO) mice and FcRn alpha-chain KO mice [1].
 

High impact information on Fcgrt

  • FcRn binds to Fc at the interface between the Fc CH2 and CH3 domains, which contains several histidine residues that could account for the sharply pH-dependent FcRn/IgG interaction [2].
  • FcRn is structurally similar to class I major histocompatibility complex (MHC) molecules, despite differences in the ligands they bind (the Fc portion of IgG and antigenic peptides, respectively) [2].
  • A low-resolution crystal structure of the complex between FcRn and Fc localizes the binding site for Fc to the side of FcRn, distinct from the tops of the alpha 1 and alpha 2 domains which serve as the peptide and T-cell receptor binding sites in class I molecules [2].
  • Fc receptors on intestinal epithelial cells of the neonatal rat (FcRn) mediate the uptake of IgG from milk [3].
  • This RNA contained functional FcRn transcripts as it encoded a beta 2-microglobulin-associated cell surface protein as determined by immunoprecipitation of biotinylated cell surface proteins with a polyclonal anti-FcRn specific antiserum [4].
 

Biological context of Fcgrt

  • Recognition of the tryptophan-based endocytosis signal in the neonatal Fc Receptor by the mu subunit of adaptor protein-2 [5].
  • These data indicate that IgG transport across alveolar epithelium takes place via regulable FcRn-mediated transcytosis, which may play an important role in alveolar homeostasis in health and disease [6].
  • This result supports a model in which IgG-induced dimerization of FcRn is relevant for signaling the cell to initiate endocytosis of the IgG-FcRn complex [7].
  • 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 [8].
  • Effects of mutations in potential phosphorylation sites on transcytosis of FcRn [9].
 

Anatomical context of Fcgrt

  • Since bile contains high levels of IgG, we sought to determine whether the FcRn was functionally expressed by adult rat hepatocytes [4].
  • FcRn, on the surface of hepatocytes, was biologically functional as it bound Fc fragments of IgG at pH 6.0 but not 8.0, which is the same pH dependence observed for FcRn in rat neonatal enterocytes [4].
  • Western blotting of hepatocyte canalicular (apical) and sinusoidal (basolateral) plasma membranes with an FcRn-specific monoclonal antibody further confirmed the protein expression and suggested that FcRn was enriched on the canalicular surface membranes [4].
  • We expressed mutant FcRn in which alanine replaced Trp-311, Leu-322, and Leu-323, or Phe-340 in the inner medullary collecting duct cell line IMCD [10].
  • In polarized cell models, FcRn in the plasma membrane is predominantly at the basolateral surface [11].
 

Associations of Fcgrt with chemical compounds

  • This suggests that hepatocyte FcRn may bind luminal IgG, providing a potential functional communication between parenchymal immune cells and bile [4].
  • Dexamethasone exposure for 72 h decreases the steady-state level of mRNA for rat FcRn alpha-subunit and the ab (but not ba) flux of biot-rIgG [6].
  • The pH dependence of IgG binding to FcRn can therefore primarily be attributed to titration of histidine residues on Fc that interact with anionic pockets on the receptor [12].
  • Individual replacement of the aromatic amino acids or the dileucine motif only partially blocked endocytosis of (125)I-Fc, whereas uptake by FcRn containing alanine residues in place of both Trp-311 and the dileucine motif was reduced to the level obtained with the tailless receptor [10].
  • The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibited basolateral to apical transport by FcRn more than apical to basolateral transport, suggesting that there are differences in the mechanisms of transport in the two directions [13].
 

Analytical, diagnostic and therapeutic context of Fcgrt

  • Affinity-purified FcRn is resolved by SDS-PAGE into components of relative molecular masses 45,000-53,000 (p51) and about 14,000 (p14) [3].
  • Using primers specific for FcRn, which did not cross hybridize with MHC class I transcripts, FcRn DNA was amplified by reverse transcriptase polymerase chain reaction from RNA of adult rat hepatocytes [4].
  • To facilitate biochemical characterization and crystallization of FcRn, we have expressed a secreted form, as well as two different lipid-linked forms solubilizable by phospholipase treatment [14].
  • Circular dichroism spectra of soluble FcRn appear similar to spectra of class I MHC molecules, suggesting that the similarities in primary sequence extend also to a similarity in secondary structure [14].
  • We show that two FcRn molecules bind per Fc, as determined by analysis of gels of washed crystals, a column binding assay, and isothermal titration calorimetry [15].

References

  1. Mechanism of hypoalbuminemia in rodents. Koltun, M., Nikolovski, J., Strong, K., Nikolic-Paterson, D., Comper, W.D. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  2. Crystal structure of the complex of rat neonatal Fc receptor with Fc. Burmeister, W.P., Huber, A.H., Bjorkman, P.J. Nature (1994) [Pubmed]
  3. An Fc receptor structurally related to MHC class I antigens. Simister, N.E., Mostov, K.E. Nature (1989) [Pubmed]
  4. A major histocompatibility complex class I-related Fc receptor for IgG on rat hepatocytes. Blumberg, R.S., Koss, T., Story, C.M., Barisani, D., Polischuk, J., Lipin, A., Pablo, L., Green, R., Simister, N.E. J. Clin. Invest. (1995) [Pubmed]
  5. Recognition of the tryptophan-based endocytosis signal in the neonatal Fc Receptor by the mu subunit of adaptor protein-2. Wernick, N.L., Haucke, V., Simister, N.E. J. Biol. Chem. (2005) [Pubmed]
  6. Net absorption of IgG via FcRn-mediated transcytosis across rat alveolar epithelial cell monolayers. Kim, K.J., Fandy, T.E., Lee, V.H., Ann, D.K., Borok, Z., Crandall, E.D. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  7. Effects of receptor dimerization on the interaction between the class I major histocompatibility complex-related Fc receptor and IgG. Raghavan, M., Wang, Y., Bjorkman, P.J. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  8. 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. Stefaner, I., Praetor, A., Hunziker, W. J. Biol. Chem. (1999) [Pubmed]
  9. Effects of mutations in potential phosphorylation sites on transcytosis of FcRn. McCarthy, K.M., Lam, M., Subramanian, L., Shakya, R., Wu, Z., Newton, E.E., Simister, N.E. J. Cell. Sci. (2001) [Pubmed]
  10. Tryptophan- and dileucine-based endocytosis signals in the neonatal Fc receptor. Wu, Z., Simister, N.E. J. Biol. Chem. (2001) [Pubmed]
  11. Characterization of basolateral-targeting signals in the neonatal Fc receptor. Newton, E.E., Wu, Z., Simister, N.E. J. Cell. Sci. (2005) [Pubmed]
  12. Structural basis of pH-dependent antibody binding by the neonatal Fc receptor. Vaughn, D.E., Bjorkman, P.J. Structure (1998) [Pubmed]
  13. Bidirectional transcytosis of IgG by the rat neonatal Fc receptor expressed in a rat kidney cell line: a system to study protein transport across epithelia. McCarthy, K.M., Yoong, Y., Simister, N.E. J. Cell. Sci. (2000) [Pubmed]
  14. Expression and crystallization of a soluble and functional form of an Fc receptor related to class I histocompatibility molecules. Gastinel, L.N., Simister, N.E., Bjorkman, P.J. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  15. Crystallization and stoichiometry of binding of a complex between a rat intestinal Fc receptor and Fc. Huber, A.H., Kelley, R.F., Gastinel, L.N., Bjorkman, P.J. J. Mol. Biol. (1993) [Pubmed]
 
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