1. Neuronal caspase 2 activity and function requires RAIDD, but not PIDD
- Author
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Elena M. Ribe, Ying Y. Jean, Carol M. Troy, Leonidas Stefanis, Rebecca L. Goldstein, Andreas Villunger, and Claudia Manzl
- 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 - 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.
- Published
- 2012