Interaction of 14-3-3 with Bid during seizure-induced neuronal death
Article first published online: 4 FEB 2004
Journal of Neurochemistry
Volume 86, Issue 2, pages 460–469, July 2003
How to Cite
Shinoda, S., Schindler, C. K., Quan-Lan, J., Saugstad, J. A., Taki, W., Simon, R. P. and Henshall, D. C. (2003), Interaction of 14-3-3 with Bid during seizure-induced neuronal death. Journal of Neurochemistry, 86: 460–469. doi: 10.1046/j.1471-4159.2003.01860.x
- Issue published online: 4 FEB 2004
- Article first published online: 4 FEB 2004
- Received February 21, 2003; revised manuscript received March 28, 2003; accepted April 15, 2003.
- BH3 domain;
Seizure-induced neuronal death may involve coordinated intracellular trafficking and protein–protein interactions of members of the Bcl-2 family. The 14-3-3 proteins are known to sequester certain pro-apoptotic members of this family. BH3-interacting domain death agonist (Bid) may contribute to seizure-induced neuronal death, although regulation by 14-3-3 has not been reported. In this study we examined whether 14-3-3 proteins interact with Bid during seizure-induced neuronal death. Brief seizures were evoked in rats by intraamygdala microinjection of kainic acid to elicit unilateral hippocampal CA3 neuronal death. Coimmunoprecipitation analysis demonstrated that although Bcl-2-associated death promoter (Bad) constitutively bound 14-3-3, there was no interaction between Bid and 14-3-3 in control brain. Seizures triggered Bid cleavage and a commensurate increase in binding of Bid to 14-3-3 within injured hippocampus. Casein kinases I and II, which can inactivate Bid by phosphoserine/threonine modification, did not coimmunoprecipitate with Bid. The largely uninjured contralateral hippocampus did not exhibit Bid cleavage or binding of 14-3-3 to Bid. In vitro experiments confirmed that 14-3-3β is capable of binding truncated Bid, likely in the absence of phosphoserine/threonine modification. These data suggest 14-3-3 proteins may target active as well as inactive conformations of pro-apoptotic Bcl-2 death agonists, highlighting novel targets for intervention in seizure-induced neuronal death.