Interaction of 14-3-3 with Bid during seizure-induced neuronal death

Sachiko Shinoda, Clara K. Schindler, Jing Quan-Lan, Julie A. Saugstad, Waro Taki, Roger P. Simon, David C. Henshall

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)460-469
Number of pages10
JournalJournal of neurochemistry
Volume86
Issue number2
DOIs
StatePublished - Jul 2003
Externally publishedYes

Keywords

  • Apoptosis
  • BH3 domain
  • Caspase
  • Epilepsy
  • Neurodegeneration
  • Rat

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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