A PARP1-ERK2 synergism is required for the induction of LTP.
Fiche publication
Date publication
avril 2016
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DANTZER Françoise
Tous les auteurs :
Visochek L, Grigoryan G, Kalal A, Milshtein-Parush H, Gazit N, Slutsky I, Yeheskel A, Shainberg A, Castiel A, Seger R, Langelier MF, Dantzer F, Pascal JM, Segal M, Cohen-Armon M
Lien Pubmed
Résumé
Unexpectedly, a post-translational modification of DNA-binding proteins, initiating the cell response to single-strand DNA damage, was also required for long-term memory acquisition in a variety of learning paradigms. Our findings disclose a molecular mechanism based on PARP1-Erk synergism, which may underlie this phenomenon. A stimulation induced PARP1 binding to phosphorylated Erk2 in the chromatin of cerebral neurons caused Erk-induced PARP1 activation, rendering transcription factors and promoters of immediate early genes (IEG) accessible to PARP1-bound phosphorylated Erk2. Thus, Erk-induced PARP1 activation mediated IEG expression implicated in long-term memory. PARP1 inhibition, silencing, or genetic deletion abrogated stimulation-induced Erk-recruitment to IEG promoters, gene expression and LTP generation in hippocampal CA3-CA1-connections. Moreover, a predominant binding of PARP1 to single-strand DNA breaks, occluding its Erk binding sites, suppressed IEG expression and prevented the generation of LTP. These findings outline a PARP1-dependent mechanism required for LTP generation, which may be implicated in long-term memory acquisition and in its deterioration in senescence.
Référence
Sci Rep. 2016 Apr;6:24950