RAIDD aggregation facilitates apoptotic death of PC12 cells and sympathetic neurons.
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.
Jabado
O
O
Department of Neurology, Columbia University, USA.
Wang
Q
Q
Rideout
H J
HJ
Yeasmin
M
M
Guo
K X
KX
Vekrellis
K
K
Papantonis
S
S
Angelastro
J M
JM
Troy
C M
CM
Stefanis
L
L
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053420:CRADD Signaling Adaptor Protein; D053143:Caspase 2; D020169:Caspases / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D013564:Sympathetic Nervous System / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D053420:CRADD Signaling Adaptor Protein; C484481:Cradd protein, mouse; C495182:Cradd protein, rat; D053143:Caspase 2; D020169:Caspases