The GDNF family: Signalling, biological functions and therapeutic value (original) (raw)
Airaksinen, M. S., Titievsky, A. & Saarma, M. GDNF family neurotrophic factor signaling: four masters, one servant? Mol. Cell. Neurosci.13, 313–325 (1999). ArticleCASPubMed Google Scholar
Baloh, R. H., Enomoto, H., Johnson, E. M. J. & Milbrandt, J. The GDNF family ligands and receptors — implications for neural development. Curr. Opin. Neurobiol.10, 103–110 (2000). ArticleCASPubMed Google Scholar
Ibáñez, C. F. Emerging themes in structural biology of neurotrophic factors. Trends Neurosci.21, 438–444 (1998). ArticlePubMed Google Scholar
Hamilton, J. F. et al. Heparin coinfusion during convection-enhanced delivery (CED) increases the distribution of the glial-derived neurotrophic factor (GDNF) ligand family in rat striatum and enhances the pharmacological activity of neurturin. Exp. Neurol.168, 155–161 (2001). ArticleCASPubMed Google Scholar
Golden, J. P., DeMaro, J. A., Osborne, P. A., Milbrandt, J. & Johnson, E. M. Jr. Expression of neurturin, GDNF, and GDNF family-receptor mRNA in the developing and mature mouse. Exp. Neurol.158, 504–528 (1999). ArticleCASPubMed Google Scholar
Lee, R., Kermani, P., Teng, K. K. & Hempstead, B. L. Regulation of cell survival by secreted proneurotrophins. Science294, 1945–1948 (2001). ArticleCASPubMed Google Scholar
Takahashi, M. The GDNF/RET signaling pathway and human diseases. Cytokine Growth Factor Rev.12, 361–373 (2001). ArticleCASPubMed Google Scholar
Lindahl, M. et al. Human glial cell line-derived neurotrophic factor receptor α4 is the receptor for persephin and is predominantly expressed in normal and malignant thyroid medullary cells. J. Biol. Chem.276, 9344–9351 (2001). ArticleCASPubMed Google Scholar
Paratcha, G. et al. Released GFRα1 potentiates downstream signaling, neuronal survival, and differentiation via a novel mechanism of recruitment of c-Ret to lipid rafts. Neuron29, 171–184 (2001).Together with reference15, this paper shows that released GFRα1–GDNF potentiates RET signalling. Moreover, it shows that RET stimulation by immobilized GFRα1–GDNF enhances axonal growth cone formation, and that soluble GFRα1 can recruit RET to lipid rafts by a novel mechanism that requires the RET tyrosine kinase. ArticleCASPubMed Google Scholar
Eketjäll, S., Fainzilber, M., Murray-Rust, J. & Ibáñez, C. F. Distinct structural elements in GDNF mediate binding to GFRα1 and activation of the GFRα1–c-Ret receptor complex. EMBO J.18, 5901–5910 (1999). ArticlePubMedPubMed Central Google Scholar
Simons, K. & Toomre, D. Lipid rafts and signal transduction. Nature Rev. Mol. Cell Biol.1, 31–39 (2000). ArticleCAS Google Scholar
Poteryaev, D. et al. GDNF triggers a novel Ret-independent Src kinase family-coupled signaling via a GPI-linked GDNF receptor α1. FEBS Lett.463, 63–66 (1999).Together with reference27, this paper provides the first demonstration that GDNF signals in a RET-independent manner through GFRα1 in lipid rafts. ArticleCASPubMed Google Scholar
Tansey, M. G., Baloh, R. H., Milbrandt, J. & Johnson, E. M. Jr. GFRα-mediated localization of RET to lipid rafts is required for effective downstream signaling, differentiation, and neuronal survival. Neuron25, 611–623 (2000).The first demonstration that the recruitment of RET to lipid rafts by GFL binding to GFRα is required for effective signalling. CASPubMed Google Scholar
Coulpier, M., Anders, J. & Ibáñez, C. F. Coordinated activation of autophosphorylation sites in the RET receptor tyrosine kinase. Importance of tyrosine 1062 for GDNF mediated neuronal differentiation and survival. J. Biol. Chem.277, 1991–1999 (2002). ArticleCASPubMed Google Scholar
Worley, D. S. et al. Developmental regulation of GDNF response and receptor expression in the enteric nervous system. Development127, 4383–4393 (2000).The first demonstration of endogenous soluble GFRα1, which is released by cultured gut cells in a developmentally regulated manner. ArticleCASPubMed Google Scholar
Manie, S., Santoro, M., Fusco, A. & Billaud, M. The RET receptor: function in development and dysfunction in congenital malformation. Trends Genet.17, 580–589 (2001). ArticleCASPubMed Google Scholar
Kaplan, D. R. & Miller, F. D. Neurotrophin signal transduction in the nervous system. Curr. Opin. Neurobiol.10, 381–391 (2000). ArticleCASPubMed Google Scholar
Yang, F. et al. PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation. Nature Neurosci.4, 19–28 (2001). ArticleCASPubMed Google Scholar
de Graaff, E. et al. Differential activities of the RET tyrosine kinase receptor isoforms during mammalian embryogenesis. Genes Dev.15, 2433–2444 (2001).Using a knock-in approach, this study shows that the short RET isoform mediates most of the biological activities of RETin vivo. ArticleCASPubMedPubMed Central Google Scholar
Tsui-Pierchala, B. A., Milbrandt, J. & Johnson, E. M. NGF utilizes c-Ret via a novel GFL-independent, inter-RTK signaling mechanism to maintain the trophic status of mature sympathetic neurons. Neuron33, 261–273 (2002).Identifies a new pathway for RET activation by NGF through TrkA. ArticleCASPubMed Google Scholar
Bordeaux, M. C. et al. The RET proto-oncogene induces apoptosis: a novel mechanism for Hirschsprung disease. EMBO J.19, 4056–4063 (2000). ArticleCASPubMedPubMed Central Google Scholar
Peterziel, H., Unsicker, K. & Krieglstein, K. Molecular mechanisms underlying the cooperative effect of glial cell line-derived neurotrophic factor and transforming growth factor-β on neurons. Soc. Neurosci. Abstr.27, 364.35 (2001). Google Scholar
Erickson, J. T., Brosenitsch, T. A. & Katz, D. M. Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor are required simultaneously for survival of dopaminergic primary sensory neurons in vivo. J. Neurosci.21, 581–589 (2001). ArticleCASPubMedPubMed Central Google Scholar
Poo, M. M. Neurotrophins as synaptic modulators. Nature Rev. Neurosci.2, 24–32 (2001). ArticleCAS Google Scholar
Fukuda, T., Kiuchi, K. & Takahashi, M. Novel mechanism of regulation of Rac activity and lamellipodia formation by RET tyrosine kinase. J. Biol. Chem. 8 March 2002 (10.1074/jbc.M200643200).
Trupp, M., Scott, R., Whittemore, S. R. & Ibáñez, C. F. Ret-dependent and -independent mechanisms of glial cell line-derived neurotrophic factor signaling in neuronal cells. J. Biol. Chem.274, 20885–20894 (1999). ArticleCASPubMed Google Scholar
Pezeshki, G., Franke, B. & Engele, J. Evidence for a ligand-specific signaling through GFRα-1, but not GFRα-2, in the absence of Ret. J. Neurosci. Res.66, 390–395 (2001). ArticleCASPubMed Google Scholar
Nishino, J. et al. GFRα3, a component of the artemin receptor, is required for migration and survival of the superior cervical ganglion. Neuron23, 725–736 (1999).The first demonstration that ARTN–GFRα3 signalling controls the migration of sympathetic precursorsin vivo. ArticleCASPubMed Google Scholar
Lindahl, M., Timmusk, T., Rossi, J., Saarma, M. & Airaksinen, M. S. Expression and alternative splicing of mouse Gfra4 suggest roles in endocrine cell development. Mol. Cell. Neurosci.15, 522–533 (2000). ArticleCASPubMed Google Scholar
Hiltunen, P. et al. Initial characterization of GDNF-family receptor GFRα4-deficient mice. Soc. Neurosci. Abstr.27, 364.31 (2001). Google Scholar
Taraviras, S. et al. Signalling by the RET receptor tyrosine kinase and its role in the development of the mammalian enteric nervous system. Development126, 2785–2797 (1999). ArticleCASPubMed Google Scholar
Homma, Y. et al. Artemin is required for the sympathetic nervous system development. Soc. Neurosci. Abstr.27, 798.4 (2001). Google Scholar
Enomoto, H. et al. RET signaling is essential for migration, axonal growth and axon guidance of developing sympathetic neurons. Development128, 3963–3974 (2001). ArticleCASPubMed Google Scholar
Andres, R. et al. Multiple effects of artemin on sympathetic neurone generation, survival and growth. Development128, 3685–3695 (2001). ArticleCASPubMed Google Scholar
Brodski, C., Schnurch, H. & Dechant, G. Neurotrophin-3 promotes the cholinergic differentiation of sympathetic neurons. Proc. Natl Acad. Sci. USA97, 9683–9688 (2000). ArticleCASPubMedPubMed Central Google Scholar
Thang, S. H., Kobayashi, M. & Matsuoka, I. Regulation of glial cell line-derived neurotrophic factor responsiveness in developing rat sympathetic neurons by retinoic acid and bone morphogenetic protein-2. J. Neurosci.20, 2917–2925 (2000). ArticleCASPubMedPubMed Central Google Scholar
Enomoto, H., Heuckeroth, R. O., Golden, J. P., Johnson, E. M. & Milbrandt, J. Development of cranial parasympathetic ganglia requires sequential actions of GDNF and neurturin. Development127, 4877–4889 (2000).Together with reference39, this paper indicates an early role for GDNF in parasympathetic precursor development. ArticleCASPubMed Google Scholar
Rossi, J., Tomac, A., Saarma, M. & Airaksinen, M. S. Distinct roles for GFRα1 and GFRα2 signalling in different cranial parasympathetic ganglia in vivo. Eur. J. Neurosci.12, 3944–3952 (2000). ArticleCASPubMed Google Scholar
Heathcote, R. D. & Sargent, P. B. Growth and morphogenesis of an autonomic ganglion. II. Establishment of neuron position. J. Neurosci.7, 2502–2509 (1987). CASPubMedPubMed Central Google Scholar
Hashino, E. et al. GDNF and neurturin are target-derived factors essential for cranial parasympathetic neuron development. Development128, 3773–3782 (2001). ArticleCASPubMed Google Scholar
Shen, L. et al. Gdnf haploinsufficiency causes Hirschsprung-like intestinal obstruction and early-onset lethality in mice. Am. J. Hum. Genet.70, 435–447 (2002). ArticleCASPubMedPubMed Central Google Scholar
Gershon, M. D. Lessons from genetically engineered animal models. II. Disorders of enteric neuronal development: insights from transgenic mice. Am. J. Physiol.277, G262–G267 (1999). ArticleCASPubMed Google Scholar
Auricchio, A. et al. Double heterozygosity for a RET substitution interfering with splicing and an EDNRB missense mutation in Hirschsprung disease. Am. J. Hum. Genet.64, 1216–1221 (1999). ArticleCASPubMedPubMed Central Google Scholar
Snider, W. D. & McMahon, S. B. Tackling pain at the source: new ideas about nociceptors. Neuron20, 629–632 (1998). ArticleCASPubMed Google Scholar
Bennett, D. L. et al. The glial cell line-derived neurotrophic factor family receptor components are differentially regulated within sensory neurons after nerve injury. J. Neurosci.20, 427–437 (2000). ArticleCASPubMedPubMed Central Google Scholar
Fundin, B. T., Mikaels, A., Westphal, H. & Ernfors, P. A rapid and dynamic regulation of GDNF-family ligands and receptors correlate with the developmental dependency of cutaneous sensory innervation. Development126, 2597–2610 (1999). ArticleCASPubMed Google Scholar
Jongen, J. L., Dalm, E., Vecht, C. J. & Holstege, J. C. Depletion of GDNF from primary afferents in adult rat dorsal horn following peripheral axotomy. Neuroreport10, 867–871 (1999). ArticleCASPubMed Google Scholar
Baudet, C. et al. Positive and negative interactions of GDNF, NTN and ART in developing sensory neuron subpopulations, and their collaboration with neurotrophins. Development127, 4335–4344 (2000). ArticleCASPubMed Google Scholar
Oppenheim, R. W. et al. Glial cell line-derived neurotrophic factor and developing mammalian motoneurons: regulation of programmed cell death among motoneuron subtypes. J. Neurosci.20, 5001–5011 (2000). ArticleCASPubMedPubMed Central Google Scholar
Stucky, C. L., Rossi, J., Airaksinen, M. S. & Lewin, G. R. The heat sensitivity of isolectin-B4 positive nociceptors is selectively lost in mice lacking the neurturin receptor GFRα2. Soc. Neurosci. Abstr.94, 8 (1999). Google Scholar
Arce, V. et al. Synergistic effects of Schwann- and muscle-derived factors on motoneuron survival involve GDNF and cardiotrophin-1 (CT-1). J. Neurosci.18, 1440–1448 (1998). ArticleCASPubMedPubMed Central Google Scholar
Keller-Peck, C. R. et al. Glial cell line-derived neurotrophic factor administration in postnatal life results in motor unit enlargement and continuous synaptic remodeling at the neuromuscular junction. J. Neurosci.21, 6136–6146 (2001). ArticleCASPubMedPubMed Central Google Scholar
Zwick, M., Teng, L., Mu, X., Springer, J. E. & Davis, B. M. Overexpression of GDNF induces and maintains hyperinnervation of muscle fibers and multiple end-plate formation. Exp. Neurol.171, 342–350 (2001). ArticleCASPubMed Google Scholar
Åkerud, P., Alberch, J., Eketjäll, S., Wagner, J. & Arenas, E. Differential effects of glial cell line-derived neurotrophic factor and neurturin on developing and adult substantia nigra dopaminergic neurons. J. Neurochem.73, 70–78 (1999). ArticlePubMed Google Scholar
Granholm, A. C. et al. Glial cell line-derived neurotrophic factor is essential for postnatal survival of midbrain dopamine neurons. J. Neurosci.20, 3182–3190 (2000). ArticleCASPubMedPubMed Central Google Scholar
Batchelor, P. E., Liberatore, G. T., Porritt, M. J., Donnan, G. A. & Howells, D. W. Inhibition of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression reduces dopaminergic sprouting in the injured striatum. Eur. J. Neurosci.12, 3462–3468 (2000). ArticleCASPubMed Google Scholar
Meng, X. et al. Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science287, 1489–1493 (2000).The first demonstration that GDNF regulates spermatogonia differentiationin vivo. ArticleCASPubMed Google Scholar
Hottinger, A. F., Azzouz, M., Deglon, N., Aebischer, P. & Zurn, A. D. Complete and long-term rescue of lesioned adult motoneurons by lentiviral-mediated expression of glial cell line-derived neurotrophic factor in the facial nucleus. J. Neurosci.20, 5587–5593 (2000). ArticleCASPubMedPubMed Central Google Scholar
Perrelet, D. et al. IAPs are essential for GDNF-mediated neuroprotective effects in injured motor neurons in vivo. Nature Cell Biol.4, 175–179 (2002).The first demonstration of a difference in trophic signalling between GFLs and neurotrophins. ArticleCASPubMed Google Scholar
Zhou, X. F., Deng, Y. S., Xian, C. J. & Zhong, J. H. Neurotrophins from dorsal root ganglia trigger allodynia after spinal nerve injury in rats. Eur. J. Neurosci.12, 100–105 (2000). ArticleCASPubMed Google Scholar
Li, L. & Zhou, X. F. Pericellular Griffonia simplicifolia I isolectin B4-binding ring structures in the dorsal root ganglia following peripheral nerve injury in rats. J. Comp. Neurol.439, 259–274 (2001). ArticleCASPubMed Google Scholar
Boucher, T. J. et al. Potent analgesic effects of GDNF in neuropathic pain states. Science290, 124–127 (2000).Shows that GDNF supresses neuropathic pain, possibly by preventing the upregulation of Na+ channel subunits. ArticleCASPubMed Google Scholar
Ramer, M. S., Priestley, J. V. & McMahon, S. B. Functional regeneration of sensory axons into the adult spinal cord. Nature403, 312–316 (2000).The first demonstration that axons can regenerate through the dorsal root entry zone into the spinal cord and form functional synapses if provided with the right growth factors. ArticleCASPubMed Google Scholar
Akkina, S. K., Patterson, C. L. & Wright, D. E. GDNF rescues nonpeptidergic unmyelinated primary afferents in streptozotocin-treated diabetic mice. Exp. Neurol.167, 173–182 (2001). ArticleCASPubMed Google Scholar
Wang, Y., Lin, S. Z., Chiou, A. L., Williams, L. R. & Hoffer, B. J. Glial cell line-derived neurotrophic factor protects against ischemia-induced injury in the cerebral cortex. J. Neurosci.17, 4341–4348 (1997). ArticleCASPubMedPubMed Central Google Scholar
Kitagawa, H. et al. Reduction of ischemic brain injury by topical application of glial cell line-derived neurotrophic factor after permanent middle cerebral artery occlusion in rats. Stroke29, 1417–1422 (1998). ArticleCASPubMed Google Scholar
Arvidsson, A., Kokaia, Z., Airaksinen, M. S., Saarma, M. & Lindvall, O. Stroke induces widespread changes of gene expression for glial cell line-derived neurotrophic factor family receptors in the adult rat brain. Neuroscience106, 27–41 (2001). ArticleCASPubMed Google Scholar
Nicole, O. et al. Neuroprotection mediated by glial cell line-derived neurotrophic factor: involvement of a reduction of NMDA-induced calcium influx by the mitogen-activated protein kinase pathway. J. Neurosci.21, 3024–3033 (2001). ArticleCASPubMedPubMed Central Google Scholar
Nanobashvili, A. et al. Development and persistence of kindling epilepsy are impaired in mice lacking glial cell line-derived neurotrophic factor family receptor α2. Proc. Natl Acad. Sci. USA97, 12312–12317 (2000). ArticleCASPubMedPubMed Central Google Scholar
Grondin, R. & Gash, D. M. Glial cell line-derived neurotrophic factor (Gdnf) — a drug candidate for the treatment of Parkinson's disease. J. Neurol.245, P35–42 (1998). ArticleCASPubMed Google Scholar
Kordower, J. H. et al. Clinicopathological findings following intraventricular glial-derived neurotrophic factor treatment in a patient with Parkinson's disease. Ann. Neurol.46, 419–424 (1999). ArticleCASPubMed Google Scholar
Kordower, J. H. et al. Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. Science290, 767–773 (2000). ArticleCASPubMed Google Scholar
Åkerud, P., Canals, J. M., Snyder, E. Y. & Arenas, E. Neuroprotection through delivery of glial cell line-derived neurotrophic factor by neural stem cells in a mouse model of Parkinson's disease. J. Neurosci.21, 8108–8118 (2001). ArticlePubMedPubMed Central Google Scholar
Björklund, A. et al. Towards a neuroprotective gene therapy for Parkinson's disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model. Brain Res.886, 82–98 (2000). ArticlePubMed Google Scholar
Zurn, A. D., Widmer, H. R. & Aebischer, P. Sustained delivery of GDNF: towards a treatment for Parkinson's disease. Brain Res. Brain Res. Rev.36, 222–229 (2001). ArticleCASPubMed Google Scholar
Nestler, E. J. Molecular basis of long-term plasticity underlying addiction. Nature Rev. Neurosci.2, 119–128 (2001). ArticleCAS Google Scholar
Messer, C. J. et al. Role for GDNF in biochemical and behavioral adaptations to drugs of abuse. Neuron26, 247–257 (2000).Indicates a role for endogenous GDNF in dopamine plasticityin vivoafter cocaine or morphine exposure. ArticleCASPubMedPubMed Central Google Scholar
Pattyn, A., Morin, X., Cremer, H., Goridis, C. & Brunet, J. F. The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives. Nature399, 366–370 (1999). ArticleCASPubMed Google Scholar
Lang, D. et al. Pax3 is required for enteric ganglia formation and functions with Sox10 to modulate expression of c-ret. J. Clin. Invest.106, 963–971 (2000). ArticleCASPubMedPubMed Central Google Scholar
Gerlai, R. et al. Impaired water maze learning performance without altered dopaminergic function in mice heterozygous for the GDNF mutation. Eur. J. Neurosci.14, 1153–1163 (2001). ArticleCASPubMed Google Scholar
Wang, C. Y. et al. Ca2+ binding protein frequenin mediates GDNF-induced potentiation of Ca2+ channels and transmitter release. Neuron32, 99–112 (2001). ArticlePubMed Google Scholar
Yang, F. et al. GDNF acutely modulates excitability and A-type K+ channels in midbrain dopaminergic neurons. Nature Neurosci.4, 1071–1078 (2001). ArticleCASPubMed Google Scholar
Scott, R. P. & Ibáñez, C. F. Determinants of ligand binding specificity in the glial cell line-derived neurotrophic factor family receptor αs. J. Biol. Chem.276, 1450–1458 (2001). ArticleCASPubMed Google Scholar
Baloh, R. H., Tansey, M. G., Johnson, E. M. J. & Milbrandt, J. Functional mapping of receptor specificity domains of glial cell line-derived neurotrophic factor (GDNF) family ligands and production of GFRα1 RET-specific agonists. J. Biol. Chem.275, 3412–3420 (2000). ArticleCASPubMed Google Scholar
Anders, J., Kjar, S. & Ibáñez, C. F. Molecular modeling of the extracellular domain of the RET receptor tyrosine kinase reveals multiple cadherin-like domains and a calcium-binding site. J. Biol. Chem.276, 35808–35817 (2001). ArticleCASPubMed Google Scholar