Abstract
Many neurons depend for their survival on retrograde signals to their cell bodies generated by nerve growth factor (NGF) or other neurotrophins at their axon terminals. Apoptosis resulting from the loss of retrograde NGF signaling contributes to the elimination of excess and misconnected neurons during development and to the death of neurons during the course of neurodegenerative diseases. Possible mechanisms of retrograde signaling include (1) retrograde transport of signaling endosomes, carrying NGF bound to activated TrkA, (2) retrograde transport of signaling molecules downstream of TrkA, and (3) retrograde propagation of a phosphorylation signal without transport of signaling molecules. Evidence is also described, which indicates that two or more retrograde signaling mechanisms exist to regulate neuronal survival, including recent evidence that withdrawal of NGF from distal axons produces a retrograde apoptotic signal, which is transported to the cell bodies, where it initiates the apoptotic program, leading to the death of the neuron.
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References
Bamji SX, Majdan M, Pozniak CD, Belliveau DJ, Aloyz R, Kohn J, Causing CG, Miller FD (1998) The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death. J Cell Biol 140:911–923
Bronfman FC, Escudero CA, Weis J, Kruttgen A (2007) Endosomal transport of neurotrophins: roles in signaling and neurodegenerative diseases. Dev Neurobiol 67:1183–1203
Campenot RB (1977) Local control of neurite development by nerve growth factor. Proc Natl Acad Sci USA 74:4516–4519
Campenot R B (1982a) Development of sympathetic neurons in compartmentalized cultures. I Local control of neurite growth by nerve growth factor. Dev Biol 93: 1–12.
Campenot R. B. (1982b) Development of sympathetic neurons in compartmentalized cultures. II. Local control of neurite survival by nerve growth factor. Dev Biol 93: 13–21.
Campenot RB (1981) Regeneration of neurites on long-term cultures of sympathetic neurons deprived of nerve growth factor. Science 214:579–581
Campenot RB (1982) Development of sympathetic neurons in compartmentalized cultures. II. Local control of neurite survival by nerve growth factor. Dev Biol 93:13–21
Cosker KE, Courchesne SL, Segal RA (2008) Action in the axon: generation and transport of signaling endosomes. Curr Opin Neurobiol 18:270–275
Cui B, Wu C, Chen L, Ramirez A, Bearer EL, Li WP, Mobley WC, Chu S (2007) One at a time, live tracking of NGF axonal transport using quantum dots. Proc Natl Acad Sci USA 104:13666–13671
Deppmann CD, Mihalas S, Sharma N, Lonze BE, Niebur E, Ginty DD (2008) A model for neuronal competition during development. Science 320:369–373
Hendry IA (1977) The effect of the retrograde axonal transport of nerve growth factor on the morphology of adrenergic neurones. Brain Res 134:213–223
Hendry IA, Stockel K, Thoenen H, Iversen LL (1974) The retrograde axonal transport of nerve growth factor. Brain Res 68:103–121
Howe CL, Mobley WC (2004) Signaling endosome hypothesis: A cellular mechanism for long distance communication. J Neurobiol 58:207–216
Ibanez CF (2007) Message in a bottle: long-range retrograde signaling in the nervous system. Trends Cell Biol 17:519–528
Kaplan DR, Hempstead BL, Martin-Zanca D, Chao MV, Parada LF (1991) The trk proto-oncogene product: A signal transducing receptor for nerve growth factor. Science 252:554–558
Kuhn TS (1962) The structure of scientific revolutions. University of Chicago Press, Chicago
Landis SC (1976) Rat sympathetic neurons and cardiac myocytes developing in microcultures: Correlation of the fine structure of endings with neurotransmitter function in single neurons. Proc Natl Acad Sci USA 73:4220–4224
MacInnis BL, Campenot RB (2002) Retrograde support of neuronal survival without retrograde transport of nerve growth factor. Science 295:1536–1539
MacInnis BL, Campenot RB (2005) Regulation of Wallerian degeneration and nerve growth factor withdrawal-induced pruning of axons of sympathetic neurons by the proteasome and the MEK/Erk pathway. Mol Cell Neurosci 28:430–439
MacInnis BL, Senger DL, Campenot RB (2003) Spatial requirements for TrkA kinase activity in the support of neuronal survival and axon growth in rat sympathetic neurons. Neuropharmacology 45:995–1010
Majdan M, Walsh GS, Aloyz R, Miller FD (2001) TrkA mediates developmental sympathetic neuron survival in vivo by silencing an ongoing p75NTR-mediated death signal. J Cell Biol 155:1275–1285
Markevich NI, Tsyganov MA, Hoek JB, Kholodenko BN (2006) Long-range signaling by phosphoprotein waves arising from bistability in protein kinase cascades. Mol Syst Biol 2:61
Mok SA, Campenot RB (2007) A nerve growth factor-induced retrograde survival signal mediated by mechanisms downstream of TrkA. Neuropharmacology 52:270–278
Mok SA, Lund K, Campenot RB (2009) A retrograde apoptotic signal originating in NGFdeprived distal axons of rat sympathetic neurons in compartmented cultures. Cell Res doi:10.1038/cr.2009.11.
Mok SA, Lund K, Campenot RB (in press) A retrograde apoptotic signal originating in NGF-deprived distal axons of rat sympathetic neurons in compartmented cultures. Cell Res; doi: 10.1038/cr.2009.11
Oppenheim RW (1991) Cell death during development of the nervous system. Annu Rev Neurosci 14:453–501
Palmada M, Kanwal S, Rutkoski NJ, Gustafson-Brown C, Johnson RS, Wisdom R, Carter BD (2002) c-jun is essential for sympathetic neuronal death induced by NGF withdrawal but not by p75 activation. J Cell Biol 158:453–461
Salehi A, Delcroix JD, Belichenko PV, Zhan K, Wu C, Valletta JS, Takimoto-Kimura R, Kleschevnikov AM, Sambamurti K, Chung PP, Xia W, Villar A, Campbell WA, Kulnane LS, Nixon RA, Lamb BT, Epstein CJ, Stokin GB, Goldstein LS, Mobley WC (2006) Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron 51:29–42
Senger DL, Campenot RB (1997) Rapid retrograde tyrosine phosphorylation of trkA and other proteins in rat sympathetic neurons in compartmented cultures. J Cell Biol 138:411–421
Toma JG, Rogers D, Senger DL, Campenot RB, Miller FD (1997) Spatial regulation of neuronal gene expression in response to nerve growth factor. Dev Biol 184:1–9
Ure DR, Campenot RB (1994) Leukemia inhibitory factor and nerve growth factor are retrogradely transported and processed by cultured rat sympathetic neurons. Dev Biol 162:339–347
Ure DR, Campenot RB (1997) Retrograde transport and steady-state distribution of 125I-nerve growth factor in rat sympathetic neurons in compartmented cultures. J Neurosci 17:1282–1290
Ure DR, Campenot RB, Acheson A (1992) Cholinergic differentiation of rat sympathetic neurons in culture: Effects of factors applied to distal neurites. Dev Biol 154:388–395
Vallee RB, Bloom GS (1991) Mechanisms of fast and slow axonal transport. Annu Rev Neurosci 14:59–92
Ye H, Kuruvilla R, Zweifel LS, Ginty DD (2003) Evidence in support of signaling endosome-based retrograde survival of sympathetic neurons. Neuron 39:57–68
Acknowledgments
Our investigations of retrograde NGF signaling in compartmented cultures represent the work of four excellent Ph.D. students: Daren Ure, Donna Senger, Bronwyn MacInnis, and Sue-Ann Mok. Excellent technical support was provided by Karen Lund, Grace Martin, Norma Jean Valli, and Megan Blacker. Financial support has been provided by the Canadian Institutes of Medical Research, The Alberta Heritage Foundation, The Alberta Paraplegic Foundation, and the Rick Hansen Man in Motion Foundation.
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© 2009 Springer-Verlag Berlin Heidelberg
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Campenot, R.B. (2009). NGF Uptake and Retrograde Signaling Mechanisms in Sympathetic Neurons in Compartmented Cultures. In: Koenig, E. (eds) Cell Biology of the Axon. Results and Problems in Cell Differentiation, vol 48. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2009_7
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DOI: https://doi.org/10.1007/400_2009_7
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