Estrogen and progesterone regulate synaptic plasticity through WAVE1 phosphorylation: rol of Cdk5 kinase.

UZAIR IVONNE DENISE; FLAMINI MARINA INES; SANCHEZ ANGEL MATIAS

Mendoza

Congreso; XXXIV Reunión Científica Anual de la Sociedad de Biología de Cuyo.; 2016

Sociedad de Biología de Cuyo

Sinaptic plasticity is the capacity of neurons of modify the function and/or structure of their dendritic spines (DS) in response to the signaling generated by neuromodulators. DS are formed by filamentous actin (F-actin) and allow synapses formation. This process is fundamental for the development of learning and memory capacities. WAVE1 protein is a well known activator of the Arp2/3 complex, a fundamental piece for actin polymerization. Our previous investigations have established that 17-β-estradiol (E2) and progesterone (P4) are important modulators that control WAVE1 phosphorylation in charge of the formation of DS. Therefore, the aim of this work were to test if Cdk5 Kinase regulates WAVE1 protein through phosphorylation events in response to rapid treatments with E2 and P4, and if this could affect the formation of DS in neuronal cells. To test our hypothesis we employed primary culture of embrionic rat cortical neurons. After neurons reached a mature state (13-14 DIV), we inhibited Cdk5 with its specific inhibitor Roscovitine and then we stimulated them with E2 and P4 for 20 min. After this treatment, we evaluated the formation of DS through Immunofluorescence and the phosphorylation pattern of WAVE1Ser397 and Cdk5Tyr15 by Western blot. Our results indicated that rapid treatments of E2 and P4 increased the number of DS in cortical neurons. Also, E2 and P4 enhanced the phosphorylation of WAVE1Ser397 and Cdk5Tyr15. In addition, treatments with Roscovitine, alone or in presence of E2 and P4, impaired WAVE1 phosphorylation and consequently the formation of DS. Our results indicated that E2 and P4 exert a dynamic control of neurons morphology by a rapid signaling to Cdk5 that modulates WAVE1 activity. This work provides a deeper understanding of the biological actions of sex steroids in the central nervous system, particularly in synaptic plasticity processes.Área temática: Biología General, Celular y Molecular (BM), Mendoza.