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Malka Cohen-Armon

Malka Cohen-Armon

Tel-Aviv University, Israel

Title: A PARP1-ERK2 synergism is required for the induction of synaptic plasticity

Biography

Cohen-Armon M has BSc in Chemistry and DSc in Physiology and Biophysics from the Technion, Israel. On 2001, she was a Visiting Researcher in Columbia University, New York, lab of Learning and Memory. She is a Faculty Member at the Tel-Aviv University Faculty of Medicine, Department of Physiology and Pharmacology and the Sagol School of Neuroscience.

Abstract

Unexpectedly, a post-translational modification of DNA-binding proteins initiating the cell response to single-strand DNA damage is also required for long-term memory acquisition in a variety of learning paradigms. Our findings disclose a molecular mechanism based on PARP1-Erk2 synergism, which can underlie this phenomenon. This mechanism is activated by a high frequency electrical stimulation inducing Erk phosphorylation. PARP1 binding to phosphorylated Erk2 via docking sites in the catalytic domain of PARP1, caused PARP1 activation that mediated the recruitment of PARP1-bound phosphorylated Erk2 to promoters of Immediate Early Genes (IEG) implicated in synaptic plasticity and long-term potentiation (LTP). PARP1 inhibition, silencing, or genetic deletion abrogated both stimulation-induced IEG expression and LTP induction. They were similarly abrogated by a predominate binding of PARP1 to single-strand DNA breaks that occluded the binding sites of Erk in PARP1. These findings outline a PARP1-dependent mechanism governing Erk-induced IEG expression implicated in synaptic plasticity. It may underlie the pivotal role of polyADP-ribosylation in long-term memory acquisition, and the deterioration in learning abilities most frequently experienced in senescence.