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Updated: May 23, 2026
08:47
Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Neuronal caspase 2 activity and function requires RAIDD, but not PIDD.
Elena M Ribe1, Ying Y Jean, Rebecca L Goldstein
1Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
The Biochemical Journal
|April 21, 2012
Summary
RAIDD, not PIDD, is essential for caspase 2 activation and neuronal death signaling. This finding clarifies the role of PIDDosome components in nerve growth factor deprivation and beta-amyloid-induced neuronal apoptosis.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Caspase 2 (CASP2) is crucial for neuronal death induced by stimuli like nerve growth factor (NGF) deprivation and beta-amyloid (Aβ).
- The PIDDosome complex (caspase 2, PIDD, RAIDD) is implicated in caspase 2 activation, but its necessity in neurons is unclear.
Purpose of the Study:
- To investigate the requirement of PIDDosome components (PIDD and RAIDD) in caspase 2 activation and execution of neuronal death.
- To elucidate the specific roles of PIDD and RAIDD in mediating neuronal apoptosis.
Main Methods:
- Examined active caspase 2 induction and neuronal death in response to NGF deprivation and Aβ treatment.
- Utilized wild-type and PIDD-null neurons to assess the necessity of PIDD and RAIDD.
- Analyzed the formation of caspase 2 and RAIDD complexes.
Main Results:
- Both NGF deprivation and Aβ treatment induce active caspase 2 in neurons.
- Caspase 2 activation and neuronal death depend on RAIDD expression but not PIDD expression.
- A complex of caspase 2 and RAIDD forms upon Aβ or NGF deprivation, even in PIDD-null neurons.
Conclusions:
- RAIDD is essential for caspase 2 activation and execution of neuronal death.
- PIDD is not required for caspase 2-dependent neuronal apoptosis.
- Caspase 2 and RAIDD function together to mediate neuronal death, independent of PIDD.
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