Alternative titles; symbols
HGNC Approved Gene Symbol: FCER1G
Cytogenetic location: 1q23.3 Genomic coordinates (GRCh38): 1:161,215,295-161,219,245 (from NCBI)
The high-affinity IgE receptor, 1 of the key molecules involved in allergic reactions, is a tetramer of 1 alpha (147140), 1 beta (147138), and 2 gamma chains. The gamma chains are also subunits of other Fc receptors.
Kuster et al. (1990) cloned and sequenced the gene for the human gamma chain.
KIR2DL4 (604945) is a member of the KIR family of natural killer (NK) cell Ig-like receptors. Using flow cytometry, Kikuchi-Maki et al. (2005) showed that cotransduction of KIR2DL4 (604945) with FCER1G promoted cell surface expression of KIR2DL4 and Ca(2+) mobilization, whereas cotransduction of KIR2DL4 with DAP10 (604089), DAP12 (TYROBP; 604142), or TCRZ (CD247; 186780) did not. Coimmunoprecipitation analysis demonstrated physical association of FCER1G with KIR2DL4. Cytotoxicity was enhanced in resting NK cells by engagement of NKp44 (NCR2; 604531), which is associated with DAP12, whereas cytotoxicity was augmented in activated NK cells by stimulating NKp46 (NCR1; 604530) or KIR2DL4, which are associated with FCER1G.
Pinheiro da Silva et al. (2007) found that Fcrg -/- mice showed reduced mortality in an acute peritonitis model caused by cecal ligation and puncture (CLP) compared with wildtype mice. The reduced mortality in Fcrg -/- mice was associated with lower serum and peritoneal Tnf (191160) and significantly increased capacity of neutrophils and macrophages to phagocytose E. coli. Fcgr3 (FCGR3A; 146740) -/- mice also had reduced sepsis after CLP. Fcgr3 bound E. coli, inducing Fcrg phosphorylation, recruitment of tyrosine phosphatase Shp1 (PTPN6; 176883), and dephosphorylation of phosphatidylinositol 3-kinase (PI3K; see 171834). Decreased Pi3k activity inhibited E. coli phagocytosis and increased Tnf production through Tlr4 (603030). Confocal microscopy demonstrated negative regulation of Marco (604870) by Fcrg. Interaction of E. coli with Fcgr3 induced recruitment of Shp1 to Marco and inhibited E. coli phagocytosis. Pinheiro da Silva et al. (2007) concluded that binding of E. coli to FCGR3 triggers an inhibitory FCRG pathway that impairs MARCO-mediated bacterial clearance and activates TNF secretion.
Kuster et al. (1990) determined that the FCER1G gene contains 5 exons and spans 4 kb. Comparison with the zeta chain of the T-cell receptor (TCRZ) indicated that these genes have evolved from a common ancestor by duplication and that they define a new gene family. Both genes are located on chromosome 1 in both mouse and human and show analogous organization of their exons. The gamma and zeta chains are essential for surface expression of their respective receptors.
By in situ hybridization, Le Coniat et al. (1990) assigned genes for both the alpha and the gamma subunits to 1q23.
Takai et al. (1994) showed that mice lacking Fcer1g developed normal numbers of mast cells but did not express Fcer1, Fcgr1 (see FCGR1A; 146760), or Fcgr3 (see FCGR3A; 146740). The mutant mice were able to bind but not phagocytose antibody-coated particles. Natural killer cell-mediated antibody-dependent cytotoxicity and mast cell-mediated allergic responses were also defective in the Fcer1g-deficient mice.
Miyajima et al. (1997) generated mice deficient in either Fcer1a or Fcer1g and mice lacking mast cells. They found that Fcer1g was required for the death and most pathophysiologic changes associated with anaphylaxis. Anaphylactic responses were often stronger in mice lacking Fcer1a and weaker in mast cell-deficient mice than in wildtype mice. Miyajima et al. (1997) proposed that IgE antibodies and Fcer1 may influence the intensity and/or kinetics of the pathophysiologic changes associated with anaphylaxis, while mortality may be mediated largely by IgG1 antibodies and Fcgr3 in mice.
Koga et al. (2004) showed that mice lacking immunoreceptor tyrosine-based activation motif (ITAM)-harboring adaptors Fc receptor common gamma subunit and Dap12 exhibit severe osteopetrosis owing to impaired osteoclast differentiation. In osteoclast precursor cells, Fc receptor-gamma and DAP12 associated with multiple immunoreceptors and activated calcium signaling through phospholipase C-gamma (see 172420). Thus, ITAM-dependent costimulatory signals activated by multiple immunoreceptors are essential for the maintenance of bone homeostasis. Koga et al. (2004) concluded that RANKL (602642) and macrophage colony-stimulating factor (120420) are not sufficient to activate the signals required for osteoclastogenesis.
Kikuchi-Maki, A., Catina, T. L., Campbell, K. S. Cutting edge: KIR2DL4 transduces signals into human NK cells through association with the Fc receptor gamma protein. J. Immun. 174: 3859-3863, 2005. [PubMed: 15778339] [Full Text: https://doi.org/10.4049/jimmunol.174.7.3859]
Koga, T., Inui, M., Inoue, K., Kim, S., Suematsu, A., Kobayashi, E., Iwata, T., Ohnishi, H., Matozaki, T., Kodama, T., Taniguchi, T., Takayanagi, H., Takai, T. Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature 428: 758-763, 2004. [PubMed: 15085135] [Full Text: https://doi.org/10.1038/nature02444]
Kuster, H., Thompson, H., Kinet, J.-P. Characterization and expression of the gene for the human Fc receptor gamma subunit: definition of a new gene family. J. Biol. Chem. 265: 6448-6452, 1990. [PubMed: 2138619]
Le Coniat, M., Kinet, J. P., Berger, R. The human genes for the alpha and gamma subunits of the mast cell receptor for immunoglobulin E are located on human chromosome band 1q23. Immunogenetics 32: 183-186, 1990. [PubMed: 2146219] [Full Text: https://doi.org/10.1007/BF02114971]
Miyajima, I., Dombrowicz, D., Martin, T. R., Ravetch, J. V., Kinet, J.-P., Galli, S. J. Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and Fc-gamma-RIII: assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE- or IgG1-dependent passive anaphylaxis. J. Clin. Invest. 99: 901-914, 1997. [PubMed: 9062348] [Full Text: https://doi.org/10.1172/JCI119255]
Pinheiro da Silva, F., Aloulou, M., Skurnik, D., Benhamou, M., Andremont, A., Velasco, I. T., Chiamolera, M., Verbeek, J. S., Launay, P., Monteiro, R. C. CD16 promotes Escherichia coli sepsis through an FcR-gamma inhibitory pathway that prevents phagocytosis and facilitates inflammation. Nature Med. 13: 1368-1374, 2007. [PubMed: 17934470] [Full Text: https://doi.org/10.1038/nm1665]
Takai, T., Li, M., Sylvestre, D., Clynes, R., Ravetch, J. V. FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell 76: 519-529, 1994. [PubMed: 8313472] [Full Text: https://doi.org/10.1016/0092-8674(94)90115-5]