title: Interaction of 14-3-3 with Bid during seizure-induced neuronal death.
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 14-3-3beta 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.
authors.affiliation: Robert S. Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon 97232, USA.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Shinoda
authors.forename: Clara K
authors.initials: CK
authors.lastname: Schindler
authors.forename: Jing
authors.initials: J
authors.lastname: Quan-Lan
authors.forename: Julie A
authors.initials: JA
authors.lastname: Saugstad
authors.forename: Waro
authors.initials: W
authors.lastname: Taki
authors.forename: Roger P
authors.initials: RP
authors.lastname: Simon
authors.forename: David C
authors.initials: DC
authors.lastname: Henshall
mesh_terms: D048948:14-3-3 Proteins; D000679:Amygdala / Q000187:drug effects; D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D047388:Casein Kinases; D003574:Cytochrome c Group / Q000032:analysis; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid; D008297:Male; D008928:Mitochondria / Q000737:chemistry / Q000201:enzymology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; C494816:Bid protein, rat; D002352:Carrier Proteins; D003574:Cytochrome c Group; D014446:Tyrosine 3-Monooxygenase; D011494:Protein Kinases; D047388:Casein Kinases; D007608:Kainic Acid