J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/01/375/14 $2.00
Volume 136, Number 2, January 27, 1997 375-388

NGF and Neurotrophin-3 Both Activate TrkA on Sympathetic Neurons but Differentially Regulate Survival and Neuritogenesis

Daniel J. Belliveau,^* Irena Krivko,^* Judi Kohn,^* Christian Lachance,^* Christine Pozniak,^* Dmitri Rusakov,^§ David Kaplan,^* and Freda D. Miller^*

^* Center for Neuronal Survival and  Brain Tumor Research Center, Montreal Neurological Institute, McGill University, Montreal, PQ, Canada H3A 2B4; and ^§ The Open University, Mylton Keynes, United Kingdom

In this report we examine the biological and molecular basis of the control of sympathetic neuron differentiation and survival by NGF and neurotrophin-3 (NT-3). NT-3 is as efficient as NGF in mediating neuritogenesis and expression of growth-associated genes in NGF-dependent sympathetic neurons, but it is 20-40fold less efficient in supporting their survival. Both NT-3 and NGF induce similar sustained, long-term activation of TrkA, while NGF is 10-fold more efficient than NT-3 in mediating acute, short-term TrkA activity. At similar acute levels of TrkA activation, NT-3 still mediates neuronal survival two- to threefold less well than NGF. However, a mutant NT-3 that activates TrkC, but not TrkA, is unable to support sympathetic neuron survival or neuritogenesis, indicating that NT3-mediated TrkA activation is necessary for both of these responses. On the basis of these data, we suggest that NGF and NT-3 differentially regulate the TrkA receptor both with regard to activation time course and downstream targets, leading to selective regulation of neuritogenesis and survival. Such differential responsiveness to two ligands acting through the same Trk receptor has important implications for neurotrophin function throughout the nervous system.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Bodmer, D., Levine-Wilkinson, S., Richmond, A., Hirsh, S., Kuruvilla, R. (2009). Wnt5a Mediates Nerve Growth Factor-Dependent Axonal Branching and Growth in Developing Sympathetic Neurons. J. Neurosci. 29: 7569-7581 [Abstract] [Full Text]  
• Deepa, S. S., Dong, L. Q. (2009). APPL1: role in adiponectin signaling and beyond. Am. J. Physiol. Endocrinol. Metab. 296: E22-E36 [Abstract] [Full Text]  
• Eldredge, L. C., Gao, X. M., Quach, D. H., Li, L., Han, X., Lomasney, J., Tourtellotte, W. G. (2008). Abnormal sympathetic nervous system development and physiological dysautonomia in Egr3-deficient mice. Development 135: 2949-2957 [Abstract] [Full Text]  
• Damon, D. H. (2008). TH and NPY in sympathetic neurovascular cultures: role of LIF and NT-3. Am. J. Physiol. Cell Physiol. 294: C306-C312 [Abstract] [Full Text]  
• Ivanisevic, L., Zheng, W., Woo, S. B., Neet, K. E., Saragovi, H. U. (2007). TrkA Receptor "Hot Spots" for Binding of NT-3 as a Heterologous Ligand. J. Biol. Chem. 282: 16754-16763 [Abstract] [Full Text]  
• Lin, D. C., Quevedo, C., Brewer, N. E., Bell, A., Testa, J. R., Grimes, M. L., Miller, F. D., Kaplan, D. R. (2006). APPL1 Associates with TrkA and GIPC1 and Is Required for Nerve Growth Factor-Mediated Signal Transduction. Mol. Cell. Biol. 26: 8928-8941 [Abstract] [Full Text]  
• Lavoie, J.-F., LeSauteur, L., Kohn, J., Wong, J., Furtoss, O., Thiele, C. J., Miller, F. D., Kaplan, D. R. (2005). TrkA Induces Apoptosis of Neuroblastoma Cells and Does So via a p53-dependent Mechanism. J. Biol. Chem. 280: 29199-29207 [Abstract] [Full Text]  
• Gandhi, R., Ryals, J. M., Wright, D. E. (2004). Neurotrophin-3 Reverses Chronic Mechanical Hyperalgesia Induced by Intramuscular Acid Injection. J. Neurosci. 24: 9405-9413 [Abstract] [Full Text]  
• Chalazonitis, A., D'Autreaux, F., Guha, U., Pham, T. D., Faure, C., Chen, J. J., Roman, D., Kan, L., Rothman, T. P., Kessler, J. A., Gershon, M. D. (2004). Bone Morphogenetic Protein-2 and -4 Limit the Number of Enteric Neurons But Promote Development of a TrkC-Expressing Neurotrophin-3-Dependent Subset. J. Neurosci. 24: 4266-4282 [Abstract] [Full Text]  
• Kim, I.-J., Drahushuk, K. M., Kim, W.-Y., Gonsiorek, E. A., Lein, P., Andres, D. A., Higgins, D. (2004). Extracellular Signal-Regulated Kinases Regulate Dendritic Growth in Rat Sympathetic Neurons. J. Neurosci. 24: 3304-3312 [Abstract] [Full Text]  
• Marsh, H. N., Dubreuil, C. I., Quevedo, C., Lee, A., Majdan, M., Walsh, G. S., Hausdorff, S., Said, F. A., Zoueva, O., Kozlowski, M., Siminovitch, K., Neel, B. G., Miller, F. D., Kaplan, D. R. (2003). SHP-1 negatively regulates neuronal survival by functioning as a TrkA phosphatase. JCB 163: 999-1010 [Abstract] [Full Text]  
• Arvanian, V. L., Horner, P. J., Gage, F. H., Mendell, L. M. (2003). Chronic Neurotrophin-3 Strengthens Synaptic Connections to Motoneurons in the Neonatal Rat. J. Neurosci. 23: 8706-8712 [Abstract] [Full Text]  
• Sayers, N. M., Beswick, L. J., Middlemas, A., Calcutt, N. A., Mizisin, A. P., Tomlinson, D. R., Fernyhough, P. (2003). Neurotrophin-3 Prevents the Proximal Accumulation of Neurofilament Proteins in Sensory Neurons of Streptozocin-Induced Diabetic Rats. Diabetes 52: 2372-2380 [Abstract] [Full Text]  
• Middlemas, A., Delcroix, J.-D., Sayers, N. M., Tomlinson, D. R., Fernyhough, P. (2003). Enhanced activation of axonally transported stress-activated protein kinases in peripheral nerve in diabetic neuropathy is prevented by neurotrophin-3. Brain 126: 1671-1682 [Abstract] [Full Text]  
• Rabin, S. J., Bachis, A., Mocchetti, I. (2002). Gangliosides Activate Trk Receptors by Inducing the Release of Neurotrophins. J. Biol. Chem. 277: 49466-49472 [Abstract] [Full Text]  
• Cupp, A. S., Tessarollo, L., Skinner, M. K. (2002). Testis Developmental Phenotypes in Neurotropin Receptor trkA and trkC Null Mutations: Role in Formation of Seminiferous Cords and Germ Cell Survival. Biol. Reprod. 66: 1838-1845 [Abstract] [Full Text]  
• Middleton, G., Davies, A. M. (2001). Populations of NGF-dependent neurones differ in their requirement for BAX to undergo apoptosis in the absence of NGF/TrkA signalling in vivo. Development 128: 4715-4728 [Abstract] [Full Text]  
• Plum, L. A., Parada, L. F., Tsoulfas, P., Clagett-Dame, M. (2001). Retinoic Acid Combined with Neurotrophin-3 Enhances the Survival and Neurite Outgrowth of Embryonic Sympathetic Neurons. Exp. Biol. Med. 226: 766-775 [Abstract] [Full Text]  
• Damon, D. H. (2001). NGF-independent survival of postganglionic sympathetic neurons in neuronal-vascular smooth muscle cocultures. Am. J. Physiol. Heart Circ. Physiol. 280: H1722-H1728 [Abstract] [Full Text]  
• Edsjö, A., Hallberg, B., Fagerström, S., Larsson, C., Axelson, H., Påhlman, S. (2001). Differences in Early and Late Responses between Neurotrophin-stimulated trkA- and trkC-transfected SH-SY5Y Neuroblastoma Cells. Cell Growth Differ. 12: 39-50 [Abstract] [Full Text]  
• Bibel, M., Barde, Y.-A. (2000). Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev. 14: 2919-2937 [Full Text]  
• Ethell, I. M., Hagihara, K., Miura, Y., Irie, F., Yamaguchi, Y. (2000). Synbindin, A Novel Syndecan-2-binding Protein in Neuronal Dendritic Spines. JCB 151: 53-68 [Abstract] [Full Text]  
• Brodski, C., Schnürch, H., Dechant, G. (2000). Neurotrophin-3 promotes the cholinergic differentiation of sympathetic neurons. Proc. Natl. Acad. Sci. USA 10.1073/pnas.160080697v1 [Abstract] [Full Text]  
• O'Connell, L., Hongo, J.-A., Presta, L. G., Tsoulfas, P. (2000). TrkA Amino Acids Controlling Specificity for Nerve Growth Factor. J. Biol. Chem. 275: 7870-7877 [Abstract] [Full Text]  
• Mazzoni, I. E., Said, F. A., Aloyz, R., Miller, F. D., Kaplan, D. (1999). Ras Regulates Sympathetic Neuron Survival by Suppressing the p53-Mediated Cell Death Pathway. J. Neurosci. 19: 9716-9727 [Abstract] [Full Text]  
• Kohn, J., Aloyz, R. S., Toma, J. G., Haak-Frendscho, M., Miller, F. D. (1999). Functionally Antagonistic Interactions between the TrkA and p75 Neurotrophin Receptors Regulate Sympathetic Neuron Growth and Target Innervation. J. Neurosci. 19: 5393-5408 [Abstract] [Full Text]  
• Yang, X.-M., Toma, J. G., Bamji, S. X., Belliveau, D. J., Kohn, J., Park, M., Miller, F. D. (1998). Autocrine Hepatocyte Growth Factor Provides a Local Mechanism for Promoting Axonal Growth. J. Neurosci. 18: 8369-8381 [Abstract] [Full Text]  
• Rochlin, M. W., Farbman, A. I. (1998). Trigeminal Ganglion Axons Are Repelled By Their Presumptive Targets. J. Neurosci. 18: 6840-6852 [Abstract] [Full Text]  
• Kobayashi, N. R., Fan, D.-P., Giehl, K. M., Bedard, A. M., Wiegand, S. J., Tetzlaff, W. (1997). BDNF and NT-4/5 Prevent Atrophy of Rat Rubrospinal Neurons after Cervical Axotomy, Stimulate GAP-43 and Talpha 1-Tubulin mRNA Expression, and Promote Axonal Regeneration. J. Neurosci. 17: 9583-9595 [Abstract] [Full Text]  
• Malcangio, M., Garrett, N. E., Cruwys, S., Tomlinson, D. R. (1997). Nerve Growth Factor- and Neurotrophin-3-Induced Changes in Nociceptive Threshold and the Release of Substance P from the Rat Isolated Spinal Cord. J. Neurosci. 17: 8459-8467 [Abstract] [Full Text]  
• Majdan, M., Lachance, C., Gloster, A., Aloyz, R., Zeindler, C., Bamji, S., Bhakar, A., Belliveau, D., Fawcett, J., Miller, F. D., Barker, P. A. (1997). Transgenic Mice Expressing the Intracellular Domain of the p75 Neurotrophin Receptor Undergo Neuronal Apoptosis. J. Neurosci. 17: 6988-6998 [Abstract] [Full Text]  
• Senger, D. L., Campenot, R. B. (1997). Rapid Retrograde Tyrosine Phosphorylation of trkA and Other Proteins in Rat Sympathetic Neurons in Compartmented Cultures. JCB 138: 411-421 [Abstract] [Full Text]  
• Dechant, G., Tsoulfas, P., Parada, L. F., Barde, Y.-A. (1997). The Neurotrophin Receptor p75 Binds Neurotrophin-3 on Sympathetic Neurons with High Affinity and Specificity. J. Neurosci. 17: 5281-5287 [Abstract] [Full Text]  
• Mischel, P. S., Smith, S. G., Vining, E. R., Valletta, J. S., Mobley, W. C., Reichardt, L. F. (2001). The Extracellular Domain of p75NTR Is Necessary to Inhibit Neurotrophin-3 Signaling through TrkA. J. Biol. Chem. 276: 11294-11301 [Abstract] [Full Text]  
• Brodski, C., Schnurch, H., Dechant, G. (2000). Neurotrophin-3 promotes the cholinergic differentiation of sympathetic neurons. Proc. Natl. Acad. Sci. USA 97: 9683-9688 [Abstract] [Full Text]  
• Orike, N., Middleton, G., Borthwick, E., Buchman, V., Cowen, T., Davies, A. M. (2001). Role of PI 3-kinase, Akt and Bcl-2-related proteins in sustaining the survival of neurotrophic factor-independent adult sympathetic neurons. JCB 154: 995-1006 [Abstract] [Full Text]  
• Majdan, M., Walsh, G. S., Aloyz, R., Miller, F. D. (2001). TrkA mediates developmental sympathetic neuron survival in vivo by silencing an ongoing p75NTR-mediated death signal. JCB 155: 1275-1286 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents