Background
Glial cell line-derived neurotrophic factor (GDNF) plays key roles in the control of vertebrate neuron survival and differentiation. A novel neurotrophic factor was recently cloned from human and mouse and designated neurturin. Physiological responses to neurturin (NTN) require the presence of receptor tyrosine kinase RET and a novel glycosylphosphatidylinositol linked receptor NTNRa. The cDNAs encoding NTNRa from human, rat, chicken, and mouse have been cloned recently and termed GDNFRb, Ret ligand 2 (RETL2) or TGF-b-related neurotrophic factor receptor 2 (TrnR2) and nominated as GFRa-2 recently. NTN binds to and forms a complex with GFRa-2 and the Ret PTK and activates the RET receptor tyrosine kinase pathway. Both NTN and GDNF can activate the MAP kinase and phosphatidylinositol 3-kinase pathways and play a critical role in the development of many neuronal populations. Neurturin and GDNF define a new family of neurotrophic factors. |
Reference
1. Kotzbauer PT, Lampe PA, Heuckeroth RO, et al. Neurturin, a relative glial-cell-line-derived neurotrophic factor. Nature 1996;384:467-470
2. Heuckeroth RO, Kotzbauer P, Copeland NG, et al. Neurturin, a novel neurotrophic factor, is localized to mouse chromosome 17 and human chromosome 19p13.3. Genomics 1997;44(1):137-40
3. Klein RD, Sherman D, Ho WH, et al. GPI-linked protein that interacts with Ret to form a candidate neurturin receptor. Nature 1997;387:717-721
4. Buj-Bello A, Adu J, Pinon LG, et al. Neurturin responsiveness requires a GPI-linked receptor and the Ret receptor tyrosine kinase. Nature 1997;387:721-724
5. Baloh RH, Tansey MG, Golden JP, et al. TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret. Neuron 1997;18:793-802
6. Sanicola M, Hession C, Worley D, et al. Glial cell line-derived neurotrophic factor-dependent RET activation can be mediated by two different cell-surface accessory proteins. Proc Natl Acad Sci
7. Suvanto P, Wartiovaara K, Lindahl M, et al. Cloning, mRNA distribution and chromosomal localisation of the gene for glial cell line-derived neurotrophic factor receptor beta, a homologue to GDNFR-alpha. Hum Mol Genet 1997;6:1267-1273
8. Wang CY, Ni J, Jiang H, et al. Cloning and characterization of glial cell line-derived neurotrophic factor receptor-B: a novel receptor for members of glial cell line-derived neurotrophic factor family of neurotrophic factors. Neuroscience 1998;83(1):7-14
9. Nomenclature Committee. Nomenclature of GPI-linked receptors for the GDNF ligand family. GFRa Neuron 1997;19:485
|
