Neonatal Fc receptor

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 is a protein that in humans is encoded by the FCGRT gene.[1][2]

The neonatal Fc receptor is an Fc receptor which is similar in structure to MHC class I. 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.[3] Further studies revealed a similar receptor in humans. 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. FcRn binds IgG at acidic pH of 6.0–6.5 but not at neutral or higher pH. Therefore, FcRn can bind IgG from the intestinal lumen (the inside of the gut) at a slightly acidic pH and ensure efficient unidirectional transport to the basolateral side (inside the body) where the pH is neutral to basic (pH 7.0–7.5).

This receptor also plays a role in adult salvage of IgG through its occurrence in the pathway of endocytosis in endothelial cells. Fc receptors in the acidic endosomes bind to IgG internalized through pinocytosis, recycling it to the cell surface, releasing it at the basic pH of blood, thereby and preventing it from undergoing lysosomal degradation. This mechanism may provide an explanation for the greater half-life of IgG in the blood compared to other isotypes.[4] It has been shown that conjugation of some drugs to the Fc domain of IgG significantly increases their half-life, likely through this mechanism.[5] There are currently five drugs on the market that have the Fc portion fused to the effector protein in order to increase its halflife. They are: Amevive (alefacept), Arcalyst (rilonacept), Enbrel (etanercept), Nplate (romiplostim) and Orencia (abatacept).

References

  1. ^ Story CM, Mikulska JE, Simister NE (December 1994). "A major histocompatibility complex class I-like Fc receptor cloned from human placenta: possible role in transfer of immunoglobulin G from mother to fetus". J. Exp. Med. 180 (6): 2377–81. doi:10.1084/jem.180.6.2377. PMC 2191771. PMID 7964511. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2191771. 
  2. ^ Kandil E, Egashira M, Miyoshi O, Niikawa N, Ishibashi T, Kasahara M, Miyosi O (1996). "The human gene encoding the heavy chain of the major histocompatibility complex class I-like Fc receptor (FCGRT) maps to 19q13.3". Cytogenet. Cell Genet. 73 (1-2): 97–8. doi:10.1159/000134316. PMID 8646894. 
  3. ^ Jones EA and Waldman TA (1972) The mechanism of intestinal uptake and transcellular transport of IgG in the neonatal rat. J Clin Invest, 51, 2916.
  4. ^ Goebl NA, Babbey CM, Datta-Mannan A, Witcher DR, Wroblewski VJ, Dunn KW (December 2008). "Neonatal Fc receptor mediates internalization of Fc in transfected human endothelial cells". Mol. Biol. Cell 19 (12): 5490–505. doi:10.1091/mbc.E07-02-0101. PMC 2592658. PMID 18843053. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2592658. 
  5. ^ Lee TY, Tjin Tham Sjin RM, Movahedi S, Ahmed B, Pravda EA, Lo KM, Gillies SD, Folkman J, Javaherian K (March 2008). "Linking antibody Fc domain to endostatin significantly improves endostatin half-life and efficacy". Clin. Cancer Res. 14 (5): 1487–93. doi:10.1158/1078-0432.CCR-07-1530. PMID 18316573. 

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