Abstract
In human cell lines, the caspase 2 adaptor RAIDD interacts selectively with caspase 2 through its caspase recruitment domain (CARD) and leads to caspase 2-dependent death. Whether RAIDD induces such effects in neuronal cells is unknown. We have previously shown that caspase 2 is essential for apoptosis of trophic factor-deprived PC12 cells and rat sympathetic neurons. We report here that rat RAIDD, cloned from PC12 cells, interacts with rat caspase 2 CARD. RAIDD overexpression induced caspase 2 CARD- and caspase 9-dependent apoptosis of PC12 cells and sympathetic neurons. Apoptosis correlated with the formation of discrete perinuclear aggregates. Both death and aggregates required the expression of full-length RAIDD. Such aggregates may enable more effective activation of caspase 2 through close proximity. Following trophic deprivation, RAIDD overexpression increased death and aggregate formation. Therefore, RAIDD aggregation is important for its death-promoting effects and may play a role in trophic factor withdrawal-induced neuronal apoptosis.
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Abbreviations
- AA:
-
amino acid
- Ab:
-
antibody
- CARD:
-
caspase recruitment domain
- DD:
-
death domain
- DED:
-
death effector domain
- MTOC:
-
microtubule organizing center
- NMR:
-
nuclear magnetic resonance
- ORF:
-
open-reading frame
- WT:
-
wild type
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Acknowledgements
This work was supported by a grant from the March of Dimes Foundation (Grant # FY99-318 to LS). Additional support was provided by a Wellcome Burroughs Career Award in Biomedical Sciences (LS), the Lowenstein, Matheson and Parkinson's Disease Foundations (LS), the NIH/NINDS (CMT) and the MDA (CMT). We would like to thank Drs. Lloyd Greene, Michael Shelanski, Isabelle Lang-Rollin and David Park for helpful discussions, Drs. Sharad Kumar and Shearwin-Whyatt for the human RAIDD construct and Dr. Philip Bird for the PAI2 construct.
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Jabado, O., Wang, Q., Rideout, H. et al. RAIDD aggregation facilitates apoptotic death of PC12 cells and sympathetic neurons. Cell Death Differ 11, 618–630 (2004). https://doi.org/10.1038/sj.cdd.4401397
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DOI: https://doi.org/10.1038/sj.cdd.4401397
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