p75 neurotrophin receptor-mediated neuronal death is promoted by Bcl-2 and prevented by Bcl-xL.
The p75 neurotrophin receptor (p75NTR) has been shown to mediate neuronal death through an unknown pathway. We microinjected p75NTR expression plasmids into sensory neurons in the presence of growth factors and assessed the effect of the expressed proteins on cell survival. We show that, unlike other members of the TNFR family, p75NTR signals death through a unique caspase-dependent death pathway that does not involve the "death domain" and is differentially regulated by Bcl-2 family members: the anti-apoptotic molecule Bcl-2 both promoted, and was required for, p75NTR killing, whereas killing was inhibited by its homologue Bcl-xL. These results demonstrate that Bcl-2, through distinct molecular mechanisms, either promotes or inhibits neuronal death depending on the nature of the death stimulus.
Coulson
E J
EJ
Walter and Eliza Hall Institute for Medical Research, Post Office, The Royal Melbourne Hospital, Parkville, Victoria, 3050, Australia.
Reid
K
K
Barrett
G L
GL
Bartlett
P F
PF
D000818:Animals; D017209:Apoptosis; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D009475:Neurons, Afferent / Q000502:physiology*; D010957:Plasmids / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D051020:bcl-X Protein