Active killing of neurons during development and following stress: A role for p75(NTR) and Fas?

Current Opinion in Neurobiology

Volumn 10, Issue 1, 2000, Pages 111-117

  Raoul, Cédric ^a   Pettmann, Brigitte ^a   Henderson, Christopher E ^a  

^a INSERM   (France)

Author keywords

[No Author keywords available]

Indexed keywords

FAS ANTIGEN; MEMBRANE PROTEIN; NEUROTROPHIN RECEPTOR; PROTEIN P75;

APOPTOSIS; NERVE CELL NECROSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION;

EID: 0033957236     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-4388(99)00055-0     Document Type: Review

References (58)

1. Pettmann B., Henderson C.E. Neuronal cell death. Neuron. 20:1998;633-647.
2. Sadoul R. Bcl-2 family members in the development and degenerative pathologies of the nervous system. Cell Death Differ. 5:1998;805-815.
3. Bibel M., Hoppe E., Barde Y.A. Biochemical and functional interactions between the neurotrophin receptors trk and p75NTR. EMBO J. 18:1999;616-622.
4. Fan G., Jaenisch R., Kucera J. A role for p75 receptor in neurotrophin-3 functioning during the development of limb proprioception. Neuroscience. 90:1999;259-268.
5. Barker P.A. p75NTR: A study in contrasts. Cell Death Differ. 5:1998;346-356.
6. Bredesen D.E., Ye X., Tasinato A., Sperandio S., Wang J.J., Assa-Munt N., Rabizadeh S. p75NTR and the concept of cellular dependence: seeing how the other half die. Cell Death Differ. 5:1998;365-371.
7. Casaccia-Bonnefil P., Kong H., Chao M.V. Neurotrophins: the biological paradox of survival factors eliciting apoptosis. Cell Death Differ. 5:1998;357-364.
8. NTR expression is not the sole determinant of susceptibility to killing by NGF, since many p75-positive, TrkA-negative cells in the CNS survive. The temporal pattern of p75-dependent cell death suggests that it could be required to provide space for axonal growth.
9. Bamji S.X., Majdan M., Pozniak C.D., Belliveau D.J., Aloyz R., Kohn J., Causing C.G., Miller F.D. The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death. J Cell Biol. 140:1998;911-923.
10. Crowley C., Spencer S.D., Nishimura M.C., Chen K.S., Pitts-Meek S., Armanini M.P., Ling L.H., MacMahon S.B., Shelton D.L., Levinson A.D.et al. Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons. Cell. 76:1994;1001-1011.
11. Van der Zee C.E., Ross G.M., Riopelle R.J., Hagg T. Survival of cholinergic forebrain neurons in developing p75NGFR- deficient mice. Science. 274:1996;1729-1732. [retracted by Hagg T in: Science 1999, 285:340].
12. Frade J.M., Rodriguez-Tebar A., Barde Y.A. Induction of cell death by endogenous nerve growth factor through its p75 receptor. Nature. 383:1996;166-168.
13. Rabizadeh S., Oh J., Zhong L.T., Yang J., Bitler C.M., Butcher L.L., Bredesen D.E. Induction of apoptosis by the low-affinity NGF receptor. Science. 261:1993;345-348.
14. Liepinsh E., Ilag L.L., Otting G., Ibanez C.F. NMR structure of the death domain of the p75 neurotrophin receptor. EMBO J. 16:1997;4999-5005.
15. Coulson E.J., Reid K., Barrett G.L., Bartlett P.F. p75 neurotrophin receptor-mediated neuronal death is promoted by Bcl-2 and prevented by Bcl-xL. J Biol Chem. 274:1999;16387-16391.
16. NTR and participates in programmed cell death. EMBO J. 18:1999;6050-6061.
17. Ferri C.C., Moore F.A., Bisby M.A. Effects of facial nerve injury on mouse motoneurons lacking the p75 low-affinity neurotrophin receptor. J Neurobiol. 34:1998;1-9.
18. Wiese S., Metzger F., Holtmann B., Sendtner M. The role of p75NTR in modulating neurotrophin survival effects in developing motoneurons. Eur J Neurosci. 11:1999;1668-1676.
19. Sendtner M., Holtmann B., Kolbeck R., Thoenen H., Barde Y.A. Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section. Nature. 360:1992;757-759.
20. Sedel F., Bechade C., Triller A. Nerve growth factor (NGF) induces motoneuron apoptosis in rat embryonic spinal cord in vitro. Eur J Neurosci. 11:1999;3904-3912.
21. Nagata S. Apoptosis by death factor. Cell. 88:1997;355-365.
22. Becher B., Barker P.A., Owens T., Antel J.P. CD95-CD95L: can the brain learn from the immune system? Trends Neurosci. 21:1998;114-117.
23. •], JNK activation itself is not sufficient to trigger cell death, since it is observed in PC12 cells maintained for long periods in NGF.
24. Brunet A., Bonni A., Zigmond M.J., Lin M.Z., Juo P., Hu L.S., Anderson M.J., Arden K.C., Blenis J., Greenberg M.E. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 96:1999;857-868. Akt is known to promote cell survival by phosphorylation of key substrates, including the Bcl-2 family member BAD, and caspase-9, both of which are components of the cell death machinery. In asking whether Akt might also indirectly down-regulate transcription of genes involved in cell death, the authors focus on the FKHRL1 transcription factor. Akt can phosphorylate FKHRL1 and by doing so promotes its retention in the cytoplasm, probably by enhancing sequestration by 14-3-3. Phosphorylation of FKHRL1 inhibits its ability to activate transcription from the Fas-L promoter, and a non-phosphorylable mutant form of FKHRL1 triggers apoptosis of cerebellar granule cells by a Fas-dependent mechanism.
25. Raoul C., Henderson C.E., Pettmann B. Programmed cell death of embryonic motoneurons triggered through the Fas death receptor. J Cell Biol. 147:1999;1049-1061. Fas, Fas-L and caspase-8 are shown to be expressed in embryonic spinal cord at the start of the developmental cell death period. In cultured motoneurons, trophic deprivation leads to the upregulation of Fas-L whereas Fas is constitutively expressed. Agents that block Fas activation or downstream steps in the Fas signalling pathway inhibit trophic deprivation-induced cell death. Exogenous Fas activators trigger motoneuron death, even in presence of optimal levels of trophic factors. However, 50% of motoneurons are resistant to Fas activation, and this figure is increased to 100% when the motoneurons are cultured for 3 days in the presence of neurotrophic factors. Resistance is correlated with strong up-regulation of FLIP, suggesting that this intracellular decoy may play an important role in controlling the Fas pathway in neurons.
26. Martin-Villalba A., Herr I., Jeremias I., Hahne M., Brandt R., Vogel J., Schenkel J., Herdegen T., Debatin K.M. CD95 Ligand (Fas-L/APO-1L) and tumor necrosis factor-related apoptosis-inducing ligand mediate ischemia-induced apoptosis in neurons. J Neurosci. 19:1999;3809-3817.
27. Herdegen T., Claret F.X., Kallunki T., Martin-Villalba A., Winter C., Hunter T., Karin M. Lasting N-terminal phosphorylation of c-Jun and activation of c-Jun N-terminal kinases after neuronal injury. J Neurosci. 18:1998;5124-5135. Nerve fibre transection and ischemia-reperfusion lead to lasting JNK activation and c-Jun amino terminal phosphorylation. In the ischemia-reperfusion model, but not that of nerve transection, there is a correlation between Fas-L expression and apoptotic cell death. This suggests that one function of phospho-c-Jun is to induce expression of Fas-L via AP-1 sites, known to be present in the Fas-L promoter. The absence of Fas-L induction following nerve fibre transection suggests that death induction by c-Jun may depend on cofactors.
28. Xia Z., Dickens M., Raingeaud J., Davis R.J., Greenberg M.E. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. 270:1995;1326-1331.
29. Eilers A., Whitfield J., Babij C., Rubin L.L., Ham J. Role of the Jun kinase pathway in the regulation of c-Jun expression and apoptosis in sympathetic neurons. J Neurosci. 18:1998;1713-1724.
30. Yang D.D., Kuan C.Y., Whitmarsh A.J., Rincon M., Zheng T.S., Davis R.J., Rakic P., Flavell R.A. Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. Nature. 389:1997;865-870.
31. Kasibhatla S., Brunner T., Genestier L., Echeverri F., Mahboubi A., Green D.R. DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T lymphocytes via the activation of NF-κB and AP-1. Mol Cell. 1:1998;543-551. This paper demonstrates the central role of NFκB and AP-1 activation in Fas-L induction during DNA-damage-induced cell apoptosis in T cells. A non-degradable mutant of IκB (inhibitory protein of NFκB) blocks Fas-L induction but not death induced by direct Fas activation. The Fas-L promoter contains NFκB and AP-1 binding sites that are necessary for the stress-induced up-regulation of Fas-L expression.
32. Kuan C.Y., Yang D.D., Samanta Roy D.R., Davis R.J., Rakic P., Flavell R.A. The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development. Neuron. 22:1999;667-676. The roles of the different members of the Jnk family in apoptosis are addressed using knockout mice. Mice deficient in Jnk1, Jnk2 or Jnk3 and double mutants for Jnk1/Jnk3 and Jnk2/Jnk3 show no development anomalies and have a normal life span, although previous work from the same group had shown that, for Jnk3 knockouts only, hippocampal neuronal death induced by kainic acid was abrogated. In contrast, Jnk1/Jnk2 double mutants show embryonic lethality at around embryonic day 11. They show region-specific dysregulation of neuronal cell death: TUNEL-positive profiles are decreased at the lateral edges of the neural tube at hindbrain levels, while PCD and levels of activated caspase-3 activity are increased in the forebrain. Thus JNKs can be involved either in apoptotic or anti-apoptotic developmental pathways depending on the context.
33. Cheema Z.F., Wade S.B., Sata M., Walsh K., Sohrabji F., Miranda R.C. Fas/Apo [Apoptosis]-1 and associated proteins in the differentiating cerebral cortex: induction of caspase-dependent cell death and activation of NF-κB. J Neurosci. 19:1999;1754-1770. This is the most complete study to date of the expression of the major components of the Fas pathway during nervous system development. There is a striking correlation between the expression of Fas and Fas-L in the developing cerebral cortex, and the period of programmed cell death in this region; expression of FLIP is also observed. In agreement with this, dissociated embryonic cortical neuroblasts can be induced to die by addition of Fas activators: soluble Fas-L or anti-Fas antibodies. Levels of Fas and FADD in embryonic cells appear to be higher in culture than in situ, suggesting that Fas expression may be repressed by the environment at earlier stages in vivo.
34. Park C., Sakamaki K., Tachibana O., Yamashima T., Yamashita J., Yonehara S. Expression of fas antigen in the normal mouse brain. Biochem Biophys Res Commun. 252:1998;623-628.
35. French L.E., Hahne M., Viard I., Radlgruber G., Zanone R., Becker K., Muller C., Tschopp J. Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover. J Cell Biol. 133:1996;335-343.
36. Sakurai M., Hayashi T., Abe K., Sadahiro M., Tabayashi K. Delayed selective motor neuron death and fas antigen induction after spinal cord ischemia in rabbits. Brain Res. 797:1998;22-28.
37. Matsuyama T., Hata R., Tagaya M., Yamamoto Y., Nakajima T., Furuyama J., Wanaka A., Sugita M. Fas antigen mRNA induction in postischemic murine brain. Brain Res. 657:1994;342-346.
38. Watanabe-Fukunaga R., Brannan C.I., Copeland N.G., Jenkins N.A., Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 356:1992;314-317.
39. Takahashi T., Tanaka M., Brannan C.I., Jenkins N.A., Copeland N.G., Suda T., Nagata S. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell. 76:1994;969-976.
40. Adachi M., Suematsu S., Kondo T., Ogasawara J., Tanaka T., Yoshida N., Nagata S. Targeted mutation in the Fas gene causes hyperplasia in peripheral lymphoid organs and liver. Nat Genet. 11:1995;294-300.
41. Irmler M., Thome M., Hahne M., Schneider P., Hofmann K., Steiner V., Bodmer J.L., Schroter M., Burns K., Mattmann C.et al. Inhibition of death receptor signals by cellular FLIP. Nature. 388:1997;190-195.
42. Yeh W.C., Pompa J.L., McCurrach M.E., Shu H.B., Elia A.J., Shahinian A., Ng M., Wakeham A., Khoo W., Mitchell K.et al. FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis. Science. 279:1998;1954-1958.
43. Varfolomeev E.E., Schuchmann M., Luria V., Chiannilkulchai N., Beckmann J.S., Mett I.L., Rebrikov D., Brodianski V.M., Kemper O.C., Kollet O.et al. Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity. 9:1998;267-276.
44. Scaffidi C., Medema J.P., Krammer P.H., Peter M.E. FLICE is predominantly expressed as two functionally active isoforms, caspase-8/a and caspase-8/b. J Biol Chem. 272:1997;26953-269538.
45. Li L., Prevette D., Oppenheim R.W., Milligan C.E. Involvement of specific caspases in motoneuron cell death in vivo and in vitro following trophic factor deprivation. Mol Cell Neurosci. 12:1998;157-167.
46. Pitti R.M., Marsters S.A., Lawrence D.A., Roy M., Kischkel F.C., Dowd P., Huang A., Donahue C.J., Sherwood S.W., Baldwin D.T.et al. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature. 396:1998;699-703.
47. Scaffidi C., Fulda S., Srinivasan A., Friesen C., Li F., Tomaselli K.J., Debatin K.M., Krammer P.H., Peter M.E. Two CD95 (APO-1/Fas) signaling pathways. EMBO J. 17:1998;1675-1687.
48. Deckwerth T.L., Elliott J.L., Knudson C.M., Johnson E.M. Jr., Snider W.D., Korsmeyer S.J. BAX is required for neuronal death after trophic factor deprivation and during development. Neuron. 17:1996;401-411.
49. Luo X., Budihardjo I., Zou H., Slaughter C., Wang X. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell. 94:1998;481-490.
50. Li H., Zhu H., Xu C.J., Yuan J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell. 94:1998;491-501.
51. Yin X.M., Wang K., Gross A., Zhao Y., Zinkel S., Klocke B., Roth K.A., Korsmeyer S.J. Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis. Nature. 400:1999;886-891.
52. Chang H.Y., Nishitoh H., Yang X., Ichijo H., Baltimore D. Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx. Science. 281:1998;1860-1863.
53. Toyoshima F., Moriguchi T., Nishida E. Fas induces cytoplasmic apoptotic responses and activation of the MKK7- JNK/SAPK and MKK6-p38 pathways independent of CPP32-like proteases. J Cell Biol. 139:1997;1005-1015.
54. Stambolic V., Suzuki A., de la Pompa J.L., Brothers G.M., Mirtsos C., Sasaki T., Ruland J., Penninger J.M., Siderovski D.P., Mak T.W. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell. 95:1998;29-39.
55. +/- lymphocytes although levels of Fas are increased, and those of Fas-L, FLIP and FADD unchanged. In contrast, Akt is hyper-phosphorylated, and its degradation by caspases impaired, suggesting that when levels of PTEN are reduced, the PI3′K/Akt survival pathway is hyper-activated. In agreement with this, PIP-3 levels are increased in mutant cells, and PI3′K inhibitors restore responsiveness to Fas. This suggests a crucial role for PTEN in Fas-triggered apoptosis, involving negative regulation of the PI3′K/Akt survival pathway.
56. Dahia P.L., Aguiar R.C., Alberta J., Kum J.B., Caron S., Sill H., Marsh D.J., Ritz J., Freedman A., Stiles C., Eng C. PTEN is inversely correlated with the cell survival factor Akt/PKB and is inactivated via multiple mechanisms in haematological malignancies. Hum Mol Genet. 8:1999;185-193.
57. Widmann C., Gibson S., Johnson G.L. Caspase-dependent cleavage of signaling proteins during apoptosis. A turn-off mechanism for anti-apoptotic signals. J Biol Chem. 273:1998;7141-7147.
58. Estevez A.G., Spear N., Manuel S.M., Radi R., Henderson C.E., Barbeito L., Beckman J.S. Nitric oxide and superoxide contribute to motor neuron apoptosis induced by trophic factor deprivation. J Neurosci. 18:1998;923-931.