Skip to main content
SpringerLink
Log in

Signaling of neuronal cell death by the p75NTR neurotrophin receptor

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The neurotrophin receptor (p75NTR) is best known for mediating tropic support by participating in the formation of high-affinity nerve growth factor (NGF) receptor complexes withtrkA, however, p75NTR more recently has been shown to act as a bona fide death-signaling receptor, which can signal independently oftrkA. This article discusses the evidence for an active role of p75NTR in neuronal cell death and the mechanisms controlling this process, including roles for Bcl-2 family members, the c-jun stress kinase JNK, the transcription factor nuclear factor kappa B (NFκB), and caspases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kaplan D. R. and Miller F. D. (1997) Signal transduction by the neurotrophin receptors.Curr. Opinion. Cell Biol. 9, 213–221.

    Article  PubMed  CAS  Google Scholar 

  2. Segal R. A., Bhattacharyya A., Rua L. A., Alberta J. A., Stephens R. M., Kaplan D. R., et al. (1996) Differential utilization of Trk autophosphorylation sites.J. Biol. Chem. 271, 20,175–20,181.

    Article  CAS  Google Scholar 

  3. Ross A. H., Daou M. C., McKinnon C. A., Condon P. J., Lachyankar M. B., Stephens R. M., et al (1996) The neurotrophin receptor, gp75, forms a complex with the receptor tyrosine kinase TrkA.J. Cell Biol. 132, 945–953.

    Article  PubMed  CAS  Google Scholar 

  4. Meakin S. O. and Shooter E. M. (1992) The nerve growth factor family of receptors.Trends Neurosci. 15, 323–331.

    Article  PubMed  CAS  Google Scholar 

  5. Huber L. J. and Chao M. V. (1995) A potential interaction of p75 and trkA NGF receptors revealed by affinity crosslinking and immunoprecipitation.J. Neurosci. Res. 40, 557–563.

    Article  PubMed  CAS  Google Scholar 

  6. Hempstead B. L., Martin-Zanca D., Kaplan D. R., Parada L. F., and Chao M. V. (1991) High-affinity NGF binding requires coexpression of the trk protooncogene and the low-affinity NGF receptor.Nature 350, 678–683.

    Article  PubMed  CAS  Google Scholar 

  7. Chao M. V. and Hempstead B. L. (1995) p75 and Trk: a two-receptor system.Trends Neurosci. 18, 321–326.

    Article  PubMed  CAS  Google Scholar 

  8. Rabizadeh S., Oh J., Zhong L. T., Yang J., Bitler C. M., Butcher L. L., et al. (1993) Induction of apoptosis by the low-affinity NGF receptor.Science 261, 345–348.

    Article  PubMed  CAS  Google Scholar 

  9. Barrett G. L. and Bartlett P. F. (1994) The p75 nerve growth factor receptor mediates survival or death depending on the stage of sensory neuron development.Proc. Natl. Acad. Sci. USA 91, 6501–6505.

    Article  PubMed  CAS  Google Scholar 

  10. Majdan M., Lachance C., Gloster A., Aloyz R., Zeindler C., Bamji S., et al. (1997) Transgenic mice expressing the intracellular domain of the p75 neurotrophin receptor undergo neuronal apoptosis.J. Neurosci. 17, 6988–6998.

    PubMed  CAS  Google Scholar 

  11. Lee K. F., Li E., Huber L. J., Landis S. C., Sharpe A. H., Chao M. V., et al. (1992) Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system.Cell 69, 737–749.

    Article  PubMed  CAS  Google Scholar 

  12. Murray S. S., Bartlett P. F., and Cheema S. S. (1999) Differential loss of spinal sensory but not motor neurons in the p75NTR knockout mouse.Neurosci. Lett.,267, 45–48.

    Article  PubMed  CAS  Google Scholar 

  13. Bamji S. X., Majdan M., Pozniak C. D., Belliveau D. J., Aloyz R., Kohn J., et al. (1998) The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death.J. Cell Biol. 140, 911–923.

    Article  PubMed  CAS  Google Scholar 

  14. Van der Zee C. E., Ross G. M., Riopelle R. J., and Hagg T. (1996) Survival of cholinergic forebrain neurons in developing p75NGFR-deficient mice.Science 274, 1729–1732.

    Article  PubMed  Google Scholar 

  15. Yeo T. T., Chua-Couzens J., Butcher L. L., Bredesen D. E., Cooper J. D., Valletta J. S., et al. (1997) Absence of p75NTR causes increased basal forebrain cholinergic neuron size, choline acetyltransferase activity, and target innervation.J. Neurosci. 17, 7594–7605.

    PubMed  CAS  Google Scholar 

  16. Coulson E. J., Reid K., Cheema S. S., and Bartlett P. F. (1999) The role of neurotrophin receptor p75NTR in mediating neuronal cell death following injury.Clin. Exp. Pharmacol. Physiol., in press.

  17. Rende M., Giambanco I., Buratta M., and Tonali P. (1995) Axotomy induces a different modulation of both low-affinity nerve growth factor receptor and choline acetyltransferase between adult rat spinal and brainstem motoneurons.J. Comp. Neurol. 363, 249–263.

    Article  PubMed  CAS  Google Scholar 

  18. Zhou X. F., Rush R. A., and McLachlan E. M. (1996) Differential expression of the p75 nerve growth factor receptor in glia and neurons of the rat dorsal root ganglia after peripheral nerve transection.J. Neurosci. 16, 2901–2911.

    PubMed  CAS  Google Scholar 

  19. Cheema S. S., Barrett G. L., and Bartlett P. F. (1996) Reducing p75 nerve growth factor receptor levels using antisense oligonucleotides prevents the loss of axotomized sensory neurons in the dorsal root ganglia of newborn rats.J. Neurosci. Res. 46, 239–245.

    Article  PubMed  CAS  Google Scholar 

  20. Ferri C. C., Moore F. A., and Bisby M. A. (1998) Effects of facial nerve injury on mouse motoneurons lacking the p75 low-affinity neurotrophin receptor.J. Neurobiol. 34, 1–9.

    Article  PubMed  CAS  Google Scholar 

  21. Murray S. S., Lopes E., Bartlett P. F., Coulsen E. J., and Cheema S. S. Unpublished observations.

  22. Richardson P. M., Issa V. M., and Riopelle R. J. (1986) Distribution of neuronal receptors for nerve growth factor in the rat.J. Neurosci. 6, 2312–2321.

    PubMed  CAS  Google Scholar 

  23. Yan Q. and Johnson E. M. Jr. (1987) A quantitative study of the developmental expression of nerve growth factor (NGF) receptor in rats.Dev. Biol. 121, 139–148.

    Article  PubMed  CAS  Google Scholar 

  24. Kerwin J. M., Morris C. M., Johnson M., Perry R. H., and Perry E. K. (1993) Hippocampal p75 nerve growth factor receptor immunoreactivity in development, normal aging and senescence.Acta Anat. 147, 216–222.

    Article  PubMed  CAS  Google Scholar 

  25. Moix L. J., Greeson D. M., Armstrong D. M., and Wiley R. G. (1991) Separate signals mediate hypoglossal motor neuron response to axonal injury.Brain Res. 564, 176–180.

    Article  PubMed  CAS  Google Scholar 

  26. Lee T. H., Abe K., Kogure K., and Itoyama Y. (1995) Expressions of nerve growth factor and p75 low affinity receptor after transient forebrain ischemia in gerbil hippocampal CA1 neurons.J. Neurosci. Res. 41, 684–695.

    Article  PubMed  CAS  Google Scholar 

  27. Wiley R. G., Berbos T. G., Deckwerth T. L., Johnson E. M. Jr., and Lappi D. A. (1995) Destruction of the cholinergic basal forebrain using immunotoxin to rat NGF receptor: modeling the cholinergic degeneration of Alzheimer's disease.J. Neurol. Sci. 128, 157–166.

    Article  PubMed  CAS  Google Scholar 

  28. Frade J. M., Rodriguez-Tebar A., and Barde Y. A. (1996) Induction of cell death by endogenous nerve growth factor through its p75 receptor.Nature 383, 166–168.

    Article  PubMed  CAS  Google Scholar 

  29. Frade J. M. and Barde Y. A. (1998) Microgliaderived nerve growth factor causes cell death in the developing retina.Neuron 20, 35–41.

    Article  PubMed  CAS  Google Scholar 

  30. Casaccia-Bonnefil P., Carter B. D., Dobrowsky R. T., and Chao M. V. (1996) Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75.Nature 383, 716–719.

    Article  PubMed  CAS  Google Scholar 

  31. Davey F. and Davies A. M. (1998) TrkB signalling inhibis p75-mediated apoptosis induced by nerve growth factor in embryonic proprioceptove neurons.Curr. Biol. 8, 915.

    Article  PubMed  CAS  Google Scholar 

  32. von Bartheld C. S., Kinoshita Y., Prevette D., Yin Q. W., Oppenheim R. W., and Bothwell M. (1994) Positive and negative effects of neurotrophins on the isthmo-optic nucleus in chick embryos.Neuron 12, 639–654.

    Article  Google Scholar 

  33. Frade J. M., Bovolenta P., Martinez-Morales J. R., Arribas A., Barbas J. A., and Rodriguez-Tebar A. (1997) Control of early cell death by BDNF in the chick retina.Development 124, 3313–3320.

    PubMed  CAS  Google Scholar 

  34. Cohen R. I., Marmur R., Norton W. T., Mehler M. F., and Kessler J. A. (1996) Nerve growth factor and neurotrophin-3 differentially regulate the proliferation and survival of developing rat brain oligodendrocytes.J. Neurosci. 16, 6433–6442.

    PubMed  CAS  Google Scholar 

  35. Yoon S. O., Casaccia-Bonnefil P., Carter B., and Chao M. V. (1998) Competitive singaling between trkA and p75 nerve growth factor receptors determines cell survival.J. Neurosci. 18, 3273–3281.

    PubMed  CAS  Google Scholar 

  36. Ladiwala U., Lachance C., Simoneau S. J., Bhakar A., Barker P. A., and Antel J. P. (1998) p75 neurotrophin receptor expression on adult human oligodendrocytes: signaling without cell death in response to NGF.J. Neurosci. 18, 1297–1304.

    PubMed  CAS  Google Scholar 

  37. Lucidi-Phillipi C. A., Clary D. O., Reichardt L. F., and Gage F. H. (1996) TrkA activation is sufficient to rescue axotomized cholinergic neurons.Neuron 16, 653–663.

    Article  PubMed  CAS  Google Scholar 

  38. Barker P. A., Barbee G., Misko T. P., and Shooter E. M. (1994) The low affinity neurotrophin receptor, p75LNTR, is palmitoylated by thioester formation through cysteine 279.J. Biol. Chem. 269, 30,645–30,650.

    CAS  Google Scholar 

  39. Canossa M., Twiss J. L., Verity A. N., and Shooter E. M. (1996) p75(NGFR) and TrkA receptors collaborate to rapidly activate a p75(NGFR)-associated protein kinase.EMBO J. 15, 3369–3376.

    PubMed  CAS  Google Scholar 

  40. Jiang Y., Woronicz J. D., Liu W., and Goeddel D. V. (1999) Prevention of constitutive TNF receptor 1 signaling by silencer of death domains.Science 283, 543–546.

    Article  PubMed  CAS  Google Scholar 

  41. Franke T. F., Kaplan D. R., and Cantley L. C. (1997) PI3K: downstream AKTion blocks apoptosis.Cell 88, 435–437.

    Article  PubMed  CAS  Google Scholar 

  42. Casaccia-Bonnefil P., Kong H., and Chao M. V. (1998) Neurotrophins: the biological paradox of survival factors eliciting apoptosis.Cell Death Differ. 5, 357–364.

    Article  PubMed  CAS  Google Scholar 

  43. Ito T., Deng X., Carr B., and May W. S. (1997) Bcl-2 phosphorylation required for antiapoptosis function.J. Biol. Chem. 272, 11,671–11,673.

    CAS  Google Scholar 

  44. Horiuchi M., Hayashida W., Kambe T., Yamada T., and Dzau V. J. (1997) Angiotensin type 2 receptor dephosphorylates Bcl-2 by activating mitogen-activated protein kinase phosphatase-1 and induces apoptosis.J. Biol. Chem. 272, 19,022–19,026.

    CAS  Google Scholar 

  45. Maundrell K., Antonsson B., Magnenat E., Camps M., Muda M., Chabert C., et al. (1997) Bcl-2 undergoes phosphorylation by c-Jun N-terminal kinase/stress-activated protein kinases in the presence of the constitutively active GTP-binding protein Rac1.J. Biol. Chem. 272, 25,238–25,242.

    Article  CAS  Google Scholar 

  46. del Peso L., Gonzalez-Garcia M., Page C., Herrera K., and Nunez G. (1997) Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt.Science 278, 687–689.

    Article  PubMed  Google Scholar 

  47. Brunet A., Bonni A., Zigmond M. J., Lin M. Z., Juo P., Hu L. S., et al. (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor.Cell 96, 857–868.

    Article  PubMed  CAS  Google Scholar 

  48. Wang C.-Y., Mayo M. W., Korneluk R. G., Goeddel D. V., and Baldwin A. S. Jr. (1998) NF-κB antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation.Science 281, 1680–1683.

    Article  PubMed  CAS  Google Scholar 

  49. Cortazzo M. H., Kassis E. S., Sproul K..A., and Schor N. F. (1996) Nerve growth factor (NGF)-mediated protection of neural crest cells from antimitotic agent-induced apoptosis: the role of the low-affinity NGF receptor.J. Neurosci. 16, 3895–3899.

    PubMed  CAS  Google Scholar 

  50. Boldin M. P., Mett I. L., Varfolomeev E. E., Chumakov I., Shemer-Avni Y., Camonis J. H., et al. (1995) Self-association of the “death domains” of the p55 tumor necrosis factor (TNF) receptor and Fas/APO1 prompts signaling for TNF and Fas/APO1 effects,J. Biol. Chem. 270, 387–391.

    Article  PubMed  CAS  Google Scholar 

  51. Mehlen P., Rabizadeh S., Snipas S. J., Assa-Munt N., Salvesen G. S., and Bredesen D. E. (1998) The DCC gene product induces apoptosis by a mechanism requiring receptor proteolysis.Nature 395, 801–804.

    Article  PubMed  CAS  Google Scholar 

  52. Rowan S. and Fisher D. E. (1997) Mechanisms of apoptotic cell death.Leukemia 11, 457–465.

    Article  PubMed  CAS  Google Scholar 

  53. Kumar S. and Lavin M. F. (1996) The ICE family of cysteine proteases as effectors of cell death.Cell Death Differ. 3, 255–267.

    PubMed  CAS  Google Scholar 

  54. Nicholson D. W. and Thornberry N. A. (1997) Caspases: Killer proteases.Trends Biochem. Sci. 22, 299–306.

    Article  PubMed  CAS  Google Scholar 

  55. Nagata S. (1997) Apoptosis by death factor.Cell 88, 355–365.

    Article  PubMed  CAS  Google Scholar 

  56. Feinstein E., Kimchi A., Wallach D., Boldin M., and Varfolomeev E. (1995) The death domain: a module shared by proteins with diverse cellular functions.Trends Biochem. Sci. 20, 342–344.

    Article  PubMed  CAS  Google Scholar 

  57. Edwards D. N., Towb P., and Wasserman S. A. (1997) An activity-dependent network of interactions links the Rel protein Dorsal with its cytoplasmic regulators.Development 124, 3855–3864.

    PubMed  CAS  Google Scholar 

  58. Coulson E. J., Reid K., Barrett G. L., and Bartlett P. F. (1999) p75NTR mediated neuronal death is promoted by Bcl-2 and prevented by Bcl-xL.J. Biol. Chem. 274, 16,387–16,391.

    Article  CAS  Google Scholar 

  59. Khursigara G., Orlinick J. R., and Chao M. V. (1999) Association of the p75NTR neurotrophin receptor with TRAF 6.J. Biol. Chem. 274, 2597–2600.

    Article  PubMed  CAS  Google Scholar 

  60. Carter B. D. and Lewin G. R. (1997) Neurotrophins live or let die: does p75NTR decide?Neuron 18, 187–190.

    Article  PubMed  CAS  Google Scholar 

  61. Liepinsh E., Ilag L. L., Otting G., and Ibanez C. F. (1997) NMR structure of the death domain of the p75 neurotrophin receptor.EMBO J. 16, 4999–5005.

    Article  PubMed  CAS  Google Scholar 

  62. Merry D. E. and Korsmeyer S. J. (1997) Bcl-2 gene family in the nervous system.Annu. Rev. Neurosci. 20, 245–267.

    Article  PubMed  CAS  Google Scholar 

  63. Reed J. C. (1997) Double identity for proteins of the Bcl-2 family.Nature 387, 773–776.

    Article  PubMed  CAS  Google Scholar 

  64. Kroemer G. (1997) The proto-oncogene Bcl-2 and its role in regulating apoptosis.Nature Med. 3, 614–620.

    Article  PubMed  CAS  Google Scholar 

  65. Zhivotovsky B., Orrenius S., Brustugun O. T., and Doskeland S. O. (1998) Injected cytochrome c induces apoptosis.Nature 391, 449,450.

    Article  PubMed  CAS  Google Scholar 

  66. Rosse T., Olivier R., Monney L., Rager M., Conus S., Fellay I., et al. (1998) Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c.Nature 391, 496–499.

    Article  PubMed  CAS  Google Scholar 

  67. Strasser A., Harris A. W., Huang D. C., Krammer P. H., and Cory S. (1995) Bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis.EMBO 14, 6136–6147.

    CAS  Google Scholar 

  68. Erhardt P. and Cooper G. M. (1996) Activation of the CPP32 apoptotic protease by distinct signaling pathways with differential sensitivity to Bcl-xL.J. Biol. Chem. 271, 17,601–17,604.

    CAS  Google Scholar 

  69. Pittman R. N., Wang S., DiBenedetto A. J., and Mills J. C. (1993) A system for characterizing cellular and molecular events in programmed neuronal cell death.J. Neurosci. 13, 3669–3680.

    PubMed  CAS  Google Scholar 

  70. Park D. S., Stefanis L., Yan C. Y. I., Farinelli S. E., and Greene L. A. (1996) Ordering the cell death pathway. Differential effects of BCL2, an interleukin-1-converting enzyme family protease inhibitor, and other survival agents on JNK activation in serum/nerve growth factor-deprived PC12 cells.J. Biol. Chem. 271, 21,898–21,905.

    CAS  Google Scholar 

  71. Deckwerth T. L., Elliott J. L., Knudson C. M., Johnson E. M. Jr., Snider W. D., and Korsmeyer S. J. (1996) BAX is required for neuronal death after trophic factor deprivation and during development.Neuron 17, 401–411.

    Article  PubMed  CAS  Google Scholar 

  72. Motoyama N., Wang F., Roth K. A., Sawa H., Nakayama K., Nakayama K., et al. (1995) Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice.Science 267, 1506–1510.

    Article  PubMed  CAS  Google Scholar 

  73. Shindler K. S., Latham C. B., and Roth K. A. (1997) Bax deficiency prevents the increased cell death of immature neurons in bcl-x-deficient mice.J. Neurosci. 17, 3112–3119.

    PubMed  CAS  Google Scholar 

  74. Nakayama K., Negishi I., Kuida K., Shinkai Y., Louie M. C., Fields L. E., et al. (1993) Disappearance of the lymphoid system in Bcl-2 homozygous mutant chimeric mice.Science 261, 1584–1588.

    Article  PubMed  CAS  Google Scholar 

  75. Veis D. J., Sorenson C. M., Shutter J. R., and Korsmeyer S. J. (1993) Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair.Cell 75, 229–240.

    Article  PubMed  CAS  Google Scholar 

  76. Merry D. E., Veis D. J., Hickey W. F., and Korsmeyer S. J. (1994) bcl-2 protein expression is widespread in the developing nervous system and retained in the adult PNS.Development 120, 301–311.

    PubMed  CAS  Google Scholar 

  77. Pinon L. G., Middleton G., and Davies A. M. (1997) Bcl-2 is required for cranial sensory neuron survival at defined stages of embryonic development.Development 124, 4173–4178.

    PubMed  CAS  Google Scholar 

  78. Allsopp T. E., Wyatt S., Paterson H. F., and Davies A. M. (1993) The proto-oncogene bcl-2 can selectively rescue neurotrophic factor-dependent neurons from apoptosis.Cell 73, 295–307.

    Article  PubMed  CAS  Google Scholar 

  79. Allsopp T. E., Kiselev S., Wyatt S., and Davies A. M. (1995) Role of Bcl-2 in the brain-derived neurotrophic factor survival response.Eur. J. Neurosci. 7, 1266–1272.

    Article  PubMed  CAS  Google Scholar 

  80. Chen J., Flannery J. G., LaVail M. M., Steinberg R. H., Xu J., and Simon M. I. (1996) bcl-2 over-expression reduces apoptotic photoreceptor cell death in three different retinal degenerations.Proc. Natl. Acad. Sci. USA 93, 7042–7047.

    Article  PubMed  CAS  Google Scholar 

  81. Farlie P. G., Dringen R., Rees S. M., Kannourakis G., and Bernard O. (1995) bcl-2 transgene expression can protect neurons against developmental and induced cell death.Proc. Natl. Acad. Sci. USA 92, 4397–4401.

    Article  PubMed  CAS  Google Scholar 

  82. Coulpier M., Junier M. P., Peschanski M., and Dreyfus P. A. (1996) Bcl-2 sensitivity differentiates two pathways for moteneuronal death in the wobbler mutant mouse.J. Neurosci. 16, 5897–5904.

    PubMed  CAS  Google Scholar 

  83. Reed J. C. (1994) Bcl-2 and the regulation of programmed cell death.J. Cell Biol. 124, 1–6.

    Article  PubMed  CAS  Google Scholar 

  84. Uhlmann E. J., Subramanian T., Vater C. A., Lutz R., and Chinnadurai G. (1998) A potent cell death activity associated with transient high level expression of BCL-2.J. Biol. Chem. 273, 17,926–17,932.

    Article  CAS  Google Scholar 

  85. Goillot E., Raingeaud J., Ranger A., Tepper R. I., Davis R. J., Harlow E., et al. (1997) Mitogenactivated protein kinase-mediated Fas apoptotic signaling pathway.Proc. Natl. Acad. Sci. USA 94, 3302–3307.

    Article  PubMed  CAS  Google Scholar 

  86. Liu Z. G., Hsu H., Goeddel D. V., and Karin M. (1996) Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-kappaB activation prevents cell death.Cell 87, 565–576.

    Article  PubMed  CAS  Google Scholar 

  87. Su Y. C., Han J., Xu S., Cobb M., and Skolnik E. Y. (1997) NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain.EMBO J. 16, 1279–1290.

    Article  PubMed  CAS  Google Scholar 

  88. Reinhard C., Shamoon B., Shyamala V., and Williams L. T. (1997) Tumor necrosis factor alpha-induced activation of c-jun N-terminal kinase is mediated by TRAF2.EMBO J. 16, 1080–1092.

    Article  PubMed  CAS  Google Scholar 

  89. Yang D. D., Kuan C. Y., Whitmarsh A. J., Rincon M., Zheng T. S., Davis R. J., Rakic P., et al. (1997) Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene.Nature 389, 865–870.

    Article  PubMed  CAS  Google Scholar 

  90. Yang X., Khosravi-Far R., Chang H. Y., and Baltimore D. (1997) Daxx, a novel Fas-binding protein that activates JNK and apoptosis.Cell 89, 1067–1076.

    Article  PubMed  CAS  Google Scholar 

  91. Nishitoh H., Saitoh M., Mochida Y., Takeda K., Nakano H., Rothe M., et al. (1998) ASK1 is essential for JNK/SAPK activation by TRAF2.Mol. Cell 2, 389–395.

    Article  PubMed  CAS  Google Scholar 

  92. Maroney A. C., Glicksman M. A., Basma A. N., Walton K. M., Knight E. Jr., Murphy C. A., et al. (1998) Motoneuron apoptosis is blocked by CEP-1347 (KT 7515), a novel inhibitor of the JNK signaling pathway.J. Neurosci. 18, 104–111.

    PubMed  CAS  Google Scholar 

  93. Deshmukh M., Vasilakos J., Deckwerth T. L., Lampe P. A., Shivers B. D., and Johnson E. M. Jr. (1996) Genetic and metabolic status of NGF-deprived sympathetic neurons saved by an inhibitor of ICE family proteases.J. Cell Biol. 135, 1341–1354.

    Article  PubMed  CAS  Google Scholar 

  94. Xia Z., Dickens M., Raingeaud J., Davis R. J., and Greenberg M. E. (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis.Science 270, 1326–1331.

    Article  PubMed  CAS  Google Scholar 

  95. Baichwal V. R. and Baeuerle P. A. (1997) Activate NF-kappa B or die?Curr. Biol. 7, R94–96.

    Article  PubMed  CAS  Google Scholar 

  96. Taglialatela G., Robinson R., and Perez-Polo J. R. (1997) Inhibition of nuclear factor kappa B (NFkappaB) activity induces nerve growth factor-resistant apoptosis in PC12 cells.J. Neurosci. Res. 47, 155–162.

    Article  PubMed  CAS  Google Scholar 

  97. Carter B. D., Kaltschmidt C., Kaltschmidt B., Offenhauser N., Bohm-Matthaei R., Baeuerle P. A., et al. (1996) Selective activation of NF-kappa B by nerve growth factor through the neurotrophin receptor p75.Science 272, 542–545.

    Article  PubMed  CAS  Google Scholar 

  98. Anton E. S., Weskamp G., Reichardt L. F., and Matthew W. D. (1994) Nerve growth factor cell migration.Proc. Natl. Acad. Sci. USA 91, 2795–2799.

    Article  PubMed  CAS  Google Scholar 

  99. Pushkareva M., Obeid L. M., and Hannun Y. A. (1995) Ceramide: an endogenous regulator of apoptosis and growth suppression.Immunol. Today 16, 294–297.

    Article  PubMed  CAS  Google Scholar 

  100. Wright S. D. and Kolesnick R. N. (1995) Does endotoxin stimulate cells by mimicking ceramide?Immunol. Today 16, 297–302.

    Article  PubMed  CAS  Google Scholar 

  101. Adam-Klages S., Adam D., Wiegmann K., Struve S., Kolanus W., Schneider-Mergener J., et al. (1996) FAN, a novel WD-repeat protein, couples the p55. TNF-receptor to neutral sphingomyelinase.Cell 86, 937–947.

    Article  PubMed  CAS  Google Scholar 

  102. Dobrowsky R. T., Werner M. H., Castellino A. M., Chao M. V., and Hannun Y. A. (1994) Activation of the sphingomyelin cycle through the low-affinity neurotrophin receptor.Science 265, 1596–1599.

    Article  PubMed  CAS  Google Scholar 

  103. Dobrowsky R. T., Jenkins G. M., and Hannun Y. A. (1995) Neurotrophins induce sphingomyelin hydrolysis. Modulation by co-expression of p75NTR with Trk receptors.J. Biol. Chem. 270, 22,135–22,142.

    CAS  Google Scholar 

  104. Gagliardini V., Fernandez P. A., Lee R. K., Drexler H. C., Rotello R. J., Fishman M. C., et al. (1994) Prevention of vertebrate neuronal death by the crmA gene.Science 263, 826–828.

    Article  PubMed  CAS  Google Scholar 

  105. Milligan C. E., Prevette D., Yaginuma H., Homma S., Cardwell C., Fritz L. C., et al. (1995) Peptide inhibitors of the ICE protease family arrest programmed cell death of motoneurons in vivo and in vitro.Neuron 15, 385–393.

    Article  PubMed  CAS  Google Scholar 

  106. Keane R. W., Srinivasan A., Foster L. M., Testa M. P., Ord T., Nonner D., et al. (1997) Activation of CPP32 during apoptosis of neurons and astrocytes.J. Neurosci. Res. 48, 168–180.

    Article  PubMed  CAS  Google Scholar 

  107. Armstrong R. C., Aja T. J., Hoang K. D., Gaur S., Bai X., Alnemri E. S., et al. (1997) Activation of the CED3/ICE-related protease CPP32 in cerebellar granule neurons undergoing apoptosis but not necrosis.J. Neurosci. 17, 553–562.

    PubMed  CAS  Google Scholar 

  108. Troy C. M., Stefanis L., Greene L. A., and Shelanski M. L. (1997) Nedd2 is required for apoptosis after trophic factor withdrawal, but not superoxide dismutase (SOD1) downregulation, in sympathetic neurons and PC12 cells.J. Neurosci. 17, 1911–1918.

    PubMed  CAS  Google Scholar 

  109. Bergeron L., Perez G. I., Macdonald G., Shi L., Sun Y., Jurisicova A., et al. (1998) Defects in regulation of apoptosis in caspase-2-deficient mice.Genes Dev. 12, 1304–1314.

    PubMed  CAS  Google Scholar 

  110. Kuida K., Zheng T. S., Na S., Kuan C., Yang D., Karasuyama H., et al. (1996) Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice.Nature 384, 368–372.

    Article  PubMed  CAS  Google Scholar 

  111. Hakem R., Hakem A., Duncan G. S., Henderson J. T., Woo M., Soengas M. S., et al. (1998) Differential requirement for caspase 9 in apoptotic pathways in vivo.Cell 94, 339–352.

    Article  PubMed  CAS  Google Scholar 

  112. Kuida K., Haydar T. F., Kuan C.-Y., Gu Y., Taya C., Karasuyama H., et al. (1998) Reduced Apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9.Cell 94, 325–337.

    Article  PubMed  CAS  Google Scholar 

  113. Yoshida H., Kong Y. Y., Yoshida R., Elia A. J., Hakem A., Hakem R., et al. (1998) Apaf1 is required for mitochondrial pathways of apoptosis and brain development.Cell 94, 739–750.

    Article  PubMed  CAS  Google Scholar 

  114. Pan G., O'Rourke K., and Dixit V. M. (1998) Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex.J. Biol. Chem. 273, 5841–5845.

    Article  PubMed  CAS  Google Scholar 

  115. Frisch S. M., Vuori K., Kelaita D., and Sicks S. (1996) A role for Jun-N-terminal kinase in anoikis; suppression by bcl-2 and crmA.J. Cell Biol. 135, 1377–1382.

    Article  PubMed  CAS  Google Scholar 

  116. Herrmann J. L., Bruckheimer E., and McDonnell T. J. (1996) Cell death signal transduction and Bcl-2 function.Biochem. Soc. Trans. 24, 1059–1065.

    PubMed  CAS  Google Scholar 

  117. Li P., Nijhawan D., Budihardjo I., Srinivasula S. M., Ahmad M., Alnemri E. S., et al. (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade.Cell 91, 479–489.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Development and Neurobiology Group, The Walter and Eliza Hall Institute of Medical Research, PO The Royal Melbourne Hospital, 3050, Parkville, Vic, Australia

    Elizabeth J. Coulson, Kate Reid & Perry F. Bartlett

Authors
  1. Elizabeth J. Coulson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kate Reid
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Perry F. Bartlett
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Coulson, E.J., Reid, K. & Bartlett, P.F. Signaling of neuronal cell death by the p75NTR neurotrophin receptor. Mol Neurobiol 20, 29–44 (1999). https://doi.org/10.1007/BF02741363

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02741363

Index Entries

Search

Navigation