Glial cell line-derived neurotrophic factor
Glial cell-derived neurotrophic factor, also known as GDNF is a protein that, in humans, is encoded by the GDNF gene.[1] GDNF is a small protein that potently promotes the survival of many types of neurons.[2]
Function
This gene encodes a highly conserved neurotrophic factor. The recombinant form of this protein was shown to promote the survival and differentiation of dopaminergic neurons in culture, and was able to prevent apoptosis of motor neurons induced by axotomy. The encoded protein is processed to a mature secreted form that exists as a homodimer. The mature form of the protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. In addition to the transcript encoding GDNF, two additional alternative transcripts encoding distinct proteins, referred to as astrocyte-derived trophic factors, have also been described. Mutations in this gene may be associated with Hirschsprung's disease.[2]
The most prominent feature of GDNF is its ability to support the survival of dopaminergic and motorneurons.
These neuronal populations die in the course of Parkinson's disease and amyotrophic lateral sclerosis (ALS). GDNF also regulates kidney development and spermatogenesis, and it affects alcohol consumption.[3]
GDNF family of ligands (GFL)
GDNF is a founding member of the GDNF family of ligands (GFL).
Interactions
Glial cell line-derived neurotrophic factor has been shown to interact with GFRA2[4][5] and GDNF family receptor alpha 1.[4][5]
References
- ^ Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F (May 1993). "GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons". Science 260 (5111): 1130–2. doi:10.1126/science.8493557. PMID 8493557. http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=8493557.
- ^ a b "Entrez Gene: GDNF glial cell derived neurotrophic factor". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2668.
- ^ Carnicella S, Kharazia V, Jeanblanc J, Janak PH, Ron D (June 2008). "GDNF is a fast-acting potent inhibitor of alcohol consumption and relapse". Proc. Natl. Acad. Sci. U.S.A. 105 (23): 8114–9. doi:10.1073/pnas.0711755105. PMC 2423415. PMID 18541917. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2423415.
- ^ a b Jing, S; Yu Y, Fang M, Hu Z, Holst P L, Boone T, Delaney J, Schultz H, Zhou R, Fox G M (Dec. 1997). "GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family". J. Biol. Chem. (UNITED STATES) 272 (52): 33111–7. doi:10.1074/jbc.272.52.33111. ISSN 0021-9258. PMID 9407096.
- ^ a b Cik, M; Masure S, Lesage A S, Van Der Linden I, Van Gompel P, Pangalos M N, Gordon R D, Leysen J E (Sep. 2000). "Binding of GDNF and neurturin to human GDNF family receptor alpha 1 and 2. Influence of cRET and cooperative interactions". J. Biol. Chem. (UNITED STATES) 275 (36): 27505–12. doi:10.1074/jbc.M000306200. ISSN 0021-9258. PMID 10829012.
Further reading
- Hofstra RM, Osinga J, Buys CH (1998). "Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype.". Eur. J. Hum. Genet. 5 (4): 180–5. PMID 9359036.
- Martucciello G, Ceccherini I, Lerone M, Jasonni V (2000). "Pathogenesis of Hirschsprung's disease.". J. Pediatr. Surg. 35 (7): 1017–25. doi:10.1053/jpsu.2000.7763. PMID 10917288.
- Schindelhauer D, Schuffenhauer S, Gasser T, et al. (1996). "The gene coding for glial cell line derived neurotrophic factor (GDNF) maps to chromosome 5p12-p13.1.". Genomics 28 (3): 605–7. doi:10.1006/geno.1995.1202. PMID 7490108.
- Tomac A, Lindqvist E, Lin LF, et al. (1995). "Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo.". Nature 373 (6512): 335–9. doi:10.1038/373335a0. PMID 7830766.
- Oppenheim RW, Houenou LJ, Johnson JE, et al. (1995). "Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF.". Nature 373 (6512): 344–6. doi:10.1038/373344a0. PMID 7830769.
- Schaar DG, Sieber BA, Sherwood AC, et al. (1995). "Multiple astrocyte transcripts encode nigral trophic factors in rat and human.". Exp. Neurol. 130 (2): 387–93. doi:10.1006/exnr.1994.1218. PMID 7867768.
- Lin LF, Doherty DH, Lile JD, et al. (1993). "GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons.". Science 260 (5111): 1130–2. doi:10.1126/science.8493557. PMID 8493557.
- Bermingham N, Hillermann R, Gilmour F, et al. (1996). "Human glial cell line-derived neurotrophic factor (GDNF) maps to chromosome 5.". Hum. Genet. 96 (6): 671–3. doi:10.1007/BF00210297. PMID 8522325.
- Gash DM, Zhang Z, Ovadia A, et al. (1996). "Functional recovery in parkinsonian monkeys treated with GDNF.". Nature 380 (6571): 252–5. doi:10.1038/380252a0. PMID 8637574.
- Jing S, Wen D, Yu Y, et al. (1996). "GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF.". Cell 85 (7): 1113–24. doi:10.1016/S0092-8674(00)81311-2. PMID 8674117.
- Angrist M, Bolk S, Halushka M, et al. (1996). "Germline mutations in glial cell line-derived neurotrophic factor (GDNF) and RET in a Hirschsprung disease patient.". Nat. Genet. 14 (3): 341–4. doi:10.1038/ng1196-341. PMID 8896568.
- Salomon R, Attié T, Pelet A, et al. (1996). "Germline mutations of the RET ligand GDNF are not sufficient to cause Hirschsprung disease.". Nat. Genet. 14 (3): 345–7. doi:10.1038/ng1196-345. PMID 8896569.
- Ivanchuk SM, Myers SM, Eng C, Mulligan LM (1997). "De novo mutation of GDNF, ligand for the RET/GDNFR-alpha receptor complex, in Hirschsprung disease.". Hum. Mol. Genet. 5 (12): 2023–6. doi:10.1093/hmg/5.12.2023. PMID 8968758.
- Haniu M, Hui J, Young Y, et al. (1997). "Glial cell line-derived neurotrophic factor: selective reduction of the intermolecular disulfide linkage and characterization of its disulfide structure.". Biochemistry 35 (51): 16799–805. doi:10.1021/bi9605550. PMID 8988018.
- Bär KJ, Facer P, Williams NS, et al. (1997). "Glial-derived neurotrophic factor in human adult and fetal intestine and in Hirschsprung's disease.". Gastroenterology 112 (4): 1381–5. doi:10.1016/S0016-5085(97)70154-9. PMID 9098026.
- Jing S, Yu Y, Fang M, et al. (1998). "GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family.". J. Biol. Chem. 272 (52): 33111–7. doi:10.1074/jbc.272.52.33111. PMID 9407096.
- Eng C, Myers SM, Kogon MD, et al. (1998). "Genomic structure and chromosomal localization of the human GDNFR-alpha gene.". Oncogene 16 (5): 597–601. doi:10.1038/sj.onc.1201573. PMID 9482105.
- Amiel J, Salomon R, Attié T, et al. (1998). "Mutations of the RET-GDNF signaling pathway in Ondine's curse.". Am. J. Hum. Genet. 62 (3): 715–7. doi:10.1086/301759. PMC 1376953. PMID 9497256. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1376953.
- Yamaguchi Y, Wada T, Suzuki F, et al. (1998). "Casein kinase II interacts with the bZIP domains of several transcription factors.". Nucleic Acids Res. 26 (16): 3854–61. doi:10.1093/nar/26.16.3854. PMC 147779. PMID 9685505. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=147779.
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PDB gallery
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1agq: GLIAL CELL-DERIVED NEUROTROPHIC FACTOR FROM RAT
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| Trk binding |
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| GFL |
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anat(h/r/t/c/b/l/s/a)/phys(r)/devp/prot/nttr/nttm/ntrp
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noco/auto/cong/tumr, sysi/epon, injr
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| Fibroblast |
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| EGF-like domain |
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| TGFβ pathway |
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| Insulin-like |
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| Platelet-derived |
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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