Год выпуска: 2012 Автор: Sanchez Angel Matias and Flamini Marina Ines Издательство: LAP Lambert Academic Publishing Страниц: 92 ISBN: 9783847317463
Описание
Estrogens are important regulators of neuronal cell morphology and this is thought to be critical for gender-specific differences in brain function and dysfunction. Dendritic spine formation is dependent on actin remodeling by WAVE1 protein, which controls actin polymerization through the Arp-2/3 complex. We show that 17-estradiol (E2) administration leads to phosphorylation and redistribution of WAVE1 at sites of dendritic spine formation. WAVE1 phosphorylation is found to be triggered by a G?i/G? protein-dependent, rapid extranuclear signaling of ER? to Src/Rac1/Cdk5 that directly phosphorylates WAVE1. After WAVE1 phosphorylation, the Arp-2/3 complex concentrates at sites of spine formation, where it triggers the local reorganization of actin fibers. In parallel, E2 recruits a G?13-dependent pathway to RhoA and ROCK-2, leading to activation of actin remodeling via moesin. Silencing of WAVE1 or of moesin abrogates the increase in dendritic spines induced by E2. In conclusion, our...