GFRA1 explained

GDNF family receptor alpha-1 (GFRα1), also known as the GDNF receptor, is a protein that in humans is encoded by the GFRA1 gene.^{[1] [2]}

Function

Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two structurally related, potent neurotrophic factors that play key roles in the control of neuron survival and differentiation. The protein encoded by this gene is a member of the GDNF receptor family. It is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor for both GDNF and NTN, and mediates activation of the RET tyrosine kinase receptor. This gene is a candidate gene for Hirschsprung disease. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.^[3]

Interactions

GDNF family receptor alpha 1 has been shown to interact with GDNF^{[4] [5]} and RET proto-oncogene.^{[5] [6]}

See also

• GFRα

Further reading

• Treanor JJ, Goodman L, de Sauvage F, Stone DM, Poulsen KT, Beck CD, Gray C, Armanini MP, Pollock RA, Hefti F, Phillips HS, Goddard A, Moore MW, Buj-Bello A, Davies AM, Asai N, Takahashi M, Vandlen R, Henderson CE, Rosenthal A . Characterization of a multicomponent receptor for GDNF . Nature . 382 . 6586 . 80–3 . Jul 1996 . 8657309 . 10.1038/382080a0 . 1996Natur.382...80T . 4253979 .
• Jing S, Wen D, Yu Y, Holst PL, Luo Y, Fang M, Tamir R, Antonio L, Hu Z, Cupples R, Louis JC, Hu S, Altrock BW, Fox GM . GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF . Cell . 85 . 7 . 1113–24 . Jun 1996 . 8674117 . 10.1016/S0092-8674(00)81311-2 . 1724567 . free .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . Sep 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Gattei V, Celetti A, Cerrato A, Degan M, De Iuliis A, Rossi FM, Chiappetta G, Consales C, Improta S, Zagonel V, Aldinucci D, Agosti V, Santoro M, Vecchio G, Pinto A, Grieco M . Expression of the RET receptor tyrosine kinase and GDNFR-alpha in normal and leukemic human hematopoietic cells and stromal cells of the bone marrow microenvironment . Blood . 89 . 8 . 2925–37 . Apr 1997 . 9108413 .
• Sanicola M, Hession C, Worley D, Carmillo P, Ehrenfels C, Walus L, Robinson S, Jaworski G, Wei H, Tizard R, Whitty A, Pepinsky RB, Cate RL . Glial cell line-derived neurotrophic factor-dependent RET activation can be mediated by two different cell-surface accessory proteins . Proceedings of the National Academy of Sciences of the United States of America . 94 . 12 . 6238–43 . Jun 1997 . 9177201 . 21033 . 10.1073/pnas.94.12.6238 . 1997PNAS...94.6238S . free .
• Baloh RH, Tansey MG, Golden JP, Creedon DJ, Heuckeroth RO, Keck CL, Zimonjic DB, Popescu NC, Johnson EM, Milbrandt J . TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret . Neuron . 18 . 5 . 793–802 . May 1997 . 9182803 . 10.1016/S0896-6273(00)80318-9 . free .
• Klein RD, Sherman D, Ho WH, Stone D, Bennett GL, Moffat B, Vandlen R, Simmons L, Gu Q, Hongo JA, Devaux B, Poulsen K, Armanini M, Nozaki C, Asai N, Goddard A, Phillips H, Henderson CE, Takahashi M, Rosenthal A . A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor . Nature . 387 . 6634 . 717–21 . Jun 1997 . 9192898 . 10.1038/42722 . 1997Natur.387..717K . 4360246 . free .
• Jing S, Yu Y, Fang M, Hu Z, Holst PL, Boone T, Delaney J, Schultz H, Zhou R, Fox GM . GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family . The Journal of Biological Chemistry . 272 . 52 . 33111–7 . Dec 1997 . 9407096 . 10.1074/jbc.272.52.33111 . free .
• Eng C, Myers SM, Kogon MD, Sanicola M, Hession C, Cate RL, Mulligan LM . Genomic structure and chromosomal localization of the human GDNFR-alpha gene . Oncogene . 16 . 5 . 597–601 . Feb 1998 . 9482105 . 10.1038/sj.onc.1201573 . 735754 .
• Shefelbine SE, Khorana S, Schultz PN, Huang E, Thobe N, Hu ZJ, Fox GM, Jing S, Cote GJ, Gagel RF . Mutational analysis of the GDNF/RET-GDNFR alpha signaling complex in a kindred with vesicoureteral reflux . Human Genetics . 102 . 4 . 474–8 . Apr 1998 . 9600247 . 10.1007/s004390050724 . 5631327 .
• Cacalano G, Fariñas I, Wang LC, Hagler K, Forgie A, Moore M, Armanini M, Phillips H, Ryan AM, Reichardt LF, Hynes M, Davies A, Rosenthal A . GFRalpha1 is an essential receptor component for GDNF in the developing nervous system and kidney . Neuron . 21 . 1 . 53–62 . Jul 1998 . 9697851 . 2710137 . 10.1016/S0896-6273(00)80514-0 .
• Enokido Y, de Sauvage F, Hongo JA, Ninkina N, Rosenthal A, Buchman VL, Davies AM . GFR alpha-4 and the tyrosine kinase Ret form a functional receptor complex for persephin . Current Biology . 8 . 18 . 1019–22 . Sep 1998 . 9740802 . 10.1016/S0960-9822(07)00422-8 . free . 1998CBio....8.1019E .
• Tansey MG, Baloh RH, Milbrandt J, Johnson EM . GFRalpha-mediated localization of RET to lipid rafts is required for effective downstream signaling, differentiation, and neuronal survival . Neuron . 25 . 3 . 611–23 . Mar 2000 . 10774729 . 10.1016/S0896-6273(00)81064-8 . free .
• Hase A, Suzuki H, Arahata K, Akazawa C . Expression of human GFR alpha-1 (GDNF receptor) at the neuromuscular junction and myelinated nerves . Neuroscience Letters . 269 . 1 . 55–7 . Jul 1999 . 10821644 . 10.1016/S0304-3940(99)00419-X . 10271/1630 . 54274004 . free .
• Cik M, Masure S, Lesage AS, Van Der Linden I, Van Gompel P, Pangalos MN, Gordon RD, Leysen JE . Binding of GDNF and neurturin to human GDNF family receptor alpha 1 and 2. Influence of cRET and cooperative interactions . The Journal of Biological Chemistry . 275 . 36 . 27505–12 . Sep 2000 . 10829012 . 10.1074/jbc.M000306200 . free .
• Paratcha G, Ledda F, Baars L, Coulpier M, Besset V, Anders J, Scott R, Ibáñez CF . Released GFRalpha1 potentiates downstream signaling, neuronal survival, and differentiation via a novel mechanism of recruitment of c-Ret to lipid rafts . Neuron . 29 . 1 . 171–84 . Jan 2001 . 11182089 . 10.1016/S0896-6273(01)00188-X . 14757558 .
• Gimm O, Dziema H, Brown J, Hoang-Vu C, Hinze R, Dralle H, Mulligan LM, Eng C . Over-representation of a germline variant in the gene encoding RET co-receptor GFRalpha-1 but not GFRalpha-2 or GFRalpha-3 in cases with sporadic medullary thyroid carcinoma . Oncogene . 20 . 17 . 2161–70 . Apr 2001 . 11360200 . 10.1038/sj.onc.1204289 . free .
• Japón MA, Urbano AG, Sáez C, Segura DI, Cerro AL, Diéguez C, Alvarez CV . Glial-derived neurotropic factor and RET gene expression in normal human anterior pituitary cell types and in pituitary tumors . The Journal of Clinical Endocrinology and Metabolism . 87 . 4 . 1879–84 . Apr 2002 . 10.1210/jcem.87.4.8383 . 11932334 . free .

Notes and References

1. Gorodinsky A, Zimonjic DB, Popescu NC, Milbrandt J . Assignment of the GDNF family receptor alpha-1 (GFRA1) to human chromosome band 10q26 by in situ hybridization . Cytogenetics and Cell Genetics . 78 . 3–4 . 289–90 . March 1998 . 9465905 . 10.1159/000134674 .
2. Angrist M, Jing S, Bolk S, Bentley K, Nallasamy S, Halushka M, Fox GM, Chakravarti A . Human GFRA1: cloning, mapping, genomic structure, and evaluation as a candidate gene for Hirschsprung disease susceptibility . Genomics . 48 . 3 . 354–62 . Mar 1998 . 9545641 . 10.1006/geno.1997.5191 .
3. Web site: Entrez Gene: GFRA1 GDNF family receptor alpha 1.
4. Jing S, Yu Y, Fang M, Hu Z, Holst PL, Boone T, Delaney J, Schultz H, Zhou R, Fox GM . GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family . The Journal of Biological Chemistry . 272 . 52 . 33111–7 . Dec 1997 . 9407096 . 10.1074/jbc.272.52.33111 . free .
5. Cik M, Masure S, Lesage AS, Van Der Linden I, Van Gompel P, Pangalos MN, Gordon RD, Leysen JE . Binding of GDNF and neurturin to human GDNF family receptor alpha 1 and 2. Influence of cRET and cooperative interactions . The Journal of Biological Chemistry . 275 . 36 . 27505–12 . Sep 2000 . 10829012 . 10.1074/jbc.M000306200 . free .
6. Klein RD, Sherman D, Ho WH, Stone D, Bennett GL, Moffat B, Vandlen R, Simmons L, Gu Q, Hongo JA, Devaux B, Poulsen K, Armanini M, Nozaki C, Asai N, Goddard A, Phillips H, Henderson CE, Takahashi M, Rosenthal A . A GPI-linked protein that interacts with Ret to form a candidate neurturin receptor . Nature . 387 . 6634 . 717–21 . Jun 1997 . 9192898 . 10.1038/42722 . 1997Natur.387..717K . 4360246 . free .