Neonatal Fc receptor
| Fc fragment of IgG, receptor, transporter, alpha | |
|---|---|
| Identifiers | |
| Symbol | FCGRT |
| Entrez | 2217 |
| HUGO | 3621 |
| OMIM | 601437 |
| RefSeq | NM_004107 |
| UniProt | P55899 |
| Other data | |
| Locus | Chr. 19 q13.3 |
The neonatal Fc receptor (FcRn), also known as the Brambell receptor, is a protein that in humans is encoded by the FCGRT gene.
The neonatal Fc receptor is an Fc receptor which is similar in structure to the MHC class I molecule and also associates with beta-2-microglobulin. It was first discovered in rodents as a unique receptor capable of transporting IgG from mother's milk across the epithelium of newborn rodent's gut into the newborn's bloodstream. Further studies revealed a similar receptor in humans, leading to the naming as a neonatal Fc receptor. In humans, however, it is found in the placenta to help facilitate transport of mother's IgG to the growing fetus and it has also been shown to play a role in monitoring IgG turnover. Neonatal Fc receptor expression is up-regulated by the proinflammatory cytokine, TNF-α, and down-regulated by IFN-γ.
FcRn helps transport IgG from the gut to the bloodstream. FcRn-mediated transcytosis of IgG across epithelial cells is possible because FcRn binds IgG at acidic pH (<6.5) but not at neutral or higher pH. Therefore, FcRn can bind IgG from the slightly acidic intestinal lumen and ensure efficient, unidirectional transport to the basolateral side where the pH is neutral to slightly basic.
This receptor also helps with the recovery of IgG in adults through the process of endocytosis in endothelial cells. FcRn in acidic endosomes bind to IgG internalized through pinocytosis, recycling it to the cell surface and releasing it at the basic pH of blood, and thereby preventing IgG from undergoing lysosomal degradation. This mechanism may provide an explanation for the greater half-life of IgG in the blood compared to that of other antibody isotypes (3 weeks). It has been shown that conjugation of some drugs to the Fc domain of IgG significantly increases their half-life.
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