Abstract
Glial cell line-derived neurotrophic factor (GDNF) was first identified as a protein with specific neurotrophic activity affecting the dopaminergic neurons of the substantia nigra.1 Since then, several studies have shown that GDNF plays an important role in mediating the survival of dopaminergic neurons.2, 3 The signal transduction pathway through which GDNF exerts this effect is thought to be GFRα-1 and Ret-dependent,4 and to involve MAP kinase and PI-3 kinase.5, 6 The tyrosine hydroxylase (TH) gene is considered to be a likely target for GDNF signaling, since intrastriatal injection of GDNF enhances nigral TH activity and dopamine content (in postnatal rats10). First discovered by Nagatsu et al. in 1964,7 TH catalyzes the rate-limiting step in catecholamine biosynthesis and since then has been the subject of numerous studies investigating the regulation of its expression and activity.8,9 The principle processes controlling the number and intrinsic catalytic activity of this enzyme include: (i) modulation of its transcription; (ii) modulation of its translation; (iii) mRNA splicing, (iv) modulation of mRNA stability; (v) phosphorylation; and (vi) feedback inhibition. Here we investigate in more detail the relationship between GDNF stimulation and TH expression.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
L.F. Lin, D.H. Doherty, J.D. Lile, S. Bektesh, and F. Collins, GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons, Science 260, 1130–1132 (1993).
D.M. Gash, Z. Zhang, A. Ovadia, W.A. Cass, A. Yi, L. Simmerman, D. Russell, D. Martin, P.A. Lapchak, F. Collins, B J. Hoffer, and G.A. Gerhardt, Functional recovery in parkinsonian monkeys treated with GDNF, Nature 380, 252–255 (1996).
C. Winkler, H. Sauer, C.S. Lee, and A. Bjorklund, Short-term GDNF treatment provides long-term rescue of lesioned nigral dopaminergic neurons in a rat model of Parkinson’s disease, J. Neurosci. 16, 7206–7215 (1996).
S. Jing, D. Wen, Y. Yu, P.L. Holst, Y. Luo, M. Fang, R. Tamir, L. Antonio, Z. Hu, R. Cupples, J.C. Louis, S. Hu, B.W. Altrock, and G.M. Fox, GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF, Cell 85, 1113–1124 (1996).
C.A. Worby, Q.C. Vega, Y. Zhao, H.H. Chao, A.F. Seasholtz, and J.E. Dixon, Glial cell line-derived neurotrophic factor signals through the RET receptor and activates mitogen-activated protein kinase. J. Biol. Chem. 271, 23619–23622 (1996).
H. Hayashi, M. Ichihara, T. Iwashita, H. Murakami, Y. Shimono, K. Kawai, K. Kurokawa, Y. Murakumo, T. Imai, H. Funahashi, A. Nakao, and M. Takahashi, Characterization of intracellular signals via tyrosine 1062 in RET activated by glial cell line-derived neurotrophic factor, Oncogene 19, 4469–4475 (2000).
T. Nagatsu, M. Levitt, and S. Udenfriend, Tyrosine hydroxylase: the initial step in norepinephrine biosynthesis, J. Biol. Chem. 239, 2910–2917 (1964).
S.C Kumer, and K.E. Vrana, Intricate regulation of tyrosine hydroxylase activity and gene expression, J. Neurochem. 67, 443–462 (1996).
T. Nagatsu, and L. Stjarne, Catecholamine synthesis and release, Adv Pharmacol. 42, 1–14 (1998).
K.D. Beck, I. Irwin, J. Valverde, T.J. Brennan, J.W. Langston, and F. Hefti, GDNF induces a dystonia-like state in neonatal rats and stimulates dopamine and serotonin synthesis, Neuron 16, 665–673 (1996).
I. Flceda, Y. Ishizaka, T. Tahira, T. Suzuki, M. Onda, T. Sugimura, and M. Nagao, Specific expression of the ret proto-oncogene in human neuroblastoma cell lines, Oncogene 5, 1291–1296 (1990).
M. Trupp, R. Scott, S.R. Whittemore, and C.F. Ibanez, Ret-dependent and -independent mechanisms of glial cell line-derived neurotrophic factor signaling in neuronal cells, J. Biol. Chem. 274, 20885–20894 (1999).
K. Miyazaki, N. Asai, T. Iwashita, M. Taniguchi, T. Isomura, H. Funahashi, H. Takagi, M. Matsuyama, and M. Takahashi, Tyrosine kinase activity of the ret proto-oncogene products in vitro, Biochem Biophys Res Commun. 193, 565–570 (1993).
M.F. Czyzyk-Krzeska, and J.E. Beresh, Characterization of the hypoxia-inducible protein binding site within the pyrimidine-rich tract in the 3’-untranslated region of the tyrosine hydroxylase mRNA, J. Biol. Chem. 271, 3293–3299 (1996).
M. Holcik, and S.A. Liebhaber, Four highly stable eukaryotic mRNAs assemble 3’ untranslated region RNA-protein complexes sharing cis and trans components, Proc. Natl. Acad. Sci. USA 94, 2410–2414 (1997).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Springer Science+Business Media New York
About this chapter
Cite this chapter
Kiuchi, K., Xiao, H. (2002). GDNF-Induced Expression of Tyrosine Hydroxylase. In: Nagatsu, T., Nabeshima, T., McCarty, R., Goldstein, D.S. (eds) Catecholamine Research. Advances in Behavioral Biology, vol 53. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-3538-3_24
Download citation
DOI: https://doi.org/10.1007/978-1-4757-3538-3_24
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4419-3388-1
Online ISBN: 978-1-4757-3538-3
eBook Packages: Springer Book Archive