Beyond Phosphorylation: ERK2 dimerization influence on memory and plasticity.

OJEA RAMOS, SANTIAGO; MEDINA, CANDELA; MILLAN, JULIETA; KRAWCZYK, MARÍA; ACUTAIN, MARÍA FLORENCIA; BAEZ, VERONICA; ROMANO, ARTURO; BOCCIA, MARIANO; FELD, MARIANA

Congreso; XXXVIII Reunion anual de la SAN; 2023

While extensive research has focused on ERK1/2 phosphorylation and its relevance tomemory and plasticity, the impact of its dimerization remains largely unexplored. Here,we study the role of ERK2 dimerization on systems with different levels of complexityusing native gel electrophoresis, behavioral and pharmacological approach. We assessthe ERK2 dimerization level during glycine-induced chemical long-term potentiation(cLTP) in mature rat cortex primary cultures, as well as in mice hippocampus followinginhibitory avoidance (IA) memory reactivation. Additionally, we assess the influence ofDEL-22379 (DEL), an ERK dimerization inhibitor that doesn’t affect phosphorylation, onIA memory reconsolidation and cLTP.Our findings reveal that ERK2 dimerization is prompted by cLTP, and this process issuppressed by DEL. We also found that, in this model, DEL is capable of inhibiting bothERK dimerization as well as phosphorylation. Furthermore, reactivating a weak IAmemory led to decreased ERK2 dimerization in IA-trained mice, while no changes werefound after a strong IA memory reactivation. We also report that when ERK2dimerization is inhibited after strong IA memory reactivation using DEL, mice behavesimilar to weak IA-trained mice.