We have previously reported that caspase 2 is essential for trophic factor deprivation-induced death of PC12 cells and sympathetic neurons (Troy et al., 1997), and that it is likely not processed by a caspase 3-like activity (Stefanis et al., 1998). The mechanisms of caspase 2 activation and its exact position within the death pathway in this model remain unclear. We have cloned by RACE the rat homologue of the caspase 2 adaptor RAIDD from PC12 cells (Yeasmin et al., SFN Abstracts 227.24, 2000). RAIDD is expressed in a predominantly cytoplasmic fashion in PC12 cells and neonatal rat sympathetic neurons. There are no observable changes in its expression or localization following trophic deprivation. Based on co-immunoprecipitation experiments however, RAIDD appears to associate with caspase 2 following serum deprivation from PC12 cells. To examine whether RAIDD is necessary for trophic deprivation-induced death, we have generated small interfering (si) RNAs directed against RAIDD. Two such siRNAs inhibit sp...