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Neuronal caspase 2 activity and function requires RAIDD, but not PIDD
- Source :
- Biochemical Journal
- Publication Year :
- 2012
- Publisher :
- Portland Press Ltd., 2012.
-
Abstract
- Caspase 2 was initially identified as a neuronally expressed developmentally down-regulated gene (HUGO gene nomenclature CASP2) and has been shown to be required for neuronal death induced by several stimuli, including NGF (nerve growth factor) deprivation and Aβ (β-amyloid). In non-neuronal cells the PIDDosome, composed of caspase 2 and two death adaptor proteins, PIDD (p53-inducible protein with a death domain) and RAIDD {RIP (receptor-interacting protein)-associated ICH-1 [ICE (interleukin-1β-converting enzyme)/CED-3 (cell-death determining 3) homologue 1] protein with a death domain}, has been proposed as the caspase 2 activation complex, although the absolute requirement for the PIDDosome is not clear. To investigate the requirement for the PIDDosome in caspase-2-dependent neuronal death, we have examined the necessity for each component in induction of active caspase 2 and in execution of caspase-2-dependent neuronal death. We find that both NGF deprivation and Aβ treatment of neurons induce active caspase 2 and that induction of this activity depends on expression of RAIDD, but is independent of PIDD expression. We show that treatment of wild-type or PIDD-null neurons with Aβ or NGF deprivation induces formation of a complex of caspase 2 and RAIDD. We also show that caspase-2-dependent execution of neurons requires RAIDD, not PIDD. Caspase 2 activity can be induced in neurons from PIDD-null mice, and NGF deprivation or Aβ use caspase 2 and RAIDD to execute death of these neurons.
- Subjects :
- Pen1, Penetratin1
Aβ, β-amyloid
CRADD Signaling Adaptor Protein
Penetratin1 small-interfering RNA (Pen1-siRNA)
PC12 Cells
Biochemistry
Rats, Sprague-Dawley
SCG, superior cervical ganglia
Mice
0302 clinical medicine
nerve growth factor deprivation
Nerve Growth Factor
Cells, Cultured
CED-3, cell-death determining 3
Mice, Knockout
Neurons
0303 health sciences
β-amyloid
NLRP1
Caspase 2
Signal transducing adaptor protein
DD, death domain
neuronal death
RIP, receptor-interacting protein
Cell biology
hippocampal neuron
AS, antisense
PIDD, p53-inducible protein with a death domain
RIP1K, RIP kinase 1
Research Article
Death Domain Receptor Signaling Adaptor Proteins
NGF, nerve growth factor
TFD, trophic factor deprivation
Biology
ERK, extracellular-signal-regulated kinase
P1, postnatal day 1
03 medical and health sciences
Enzyme activator
RAIDD, RIP (receptor-interacting protein)-associated ICH-1 [ICE (interleukin-1β-converting enzyme)/CED-3 homologue 1] protein with a DD
HFIP, 1,1,1,3,3,3 hexafluoro-2-propanol
Animals
CARD, caspase-recruitment domain
Molecular Biology
030304 developmental biology
Death domain
sympathetic neuron
Cell Biology
PIDDosome
biotin-VAD-FMK, biotin-Val-Ala-DL-Asp-fluoromethylketone
Rats
Enzyme Activation
Nerve growth factor
Animals, Newborn
nervous system
siRNA, small interfering RNA
biology.protein
Caspase 10
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14708728 and 02646021
- Volume :
- 444
- Database :
- OpenAIRE
- Journal :
- Biochemical Journal
- Accession number :
- edsair.doi.dedup.....93de2ecdbf33676c34d49020da224c71