Estradiol regulates actin polymerization and axonal branching in neuronal cells via a rapid activation of WAVE1.

A.M. SANCHEZ; M.I. FLAMINI; A.R. GENAZZANI; T. SIMONCINI

September 24-27, Orlando, Florida, USA

Congreso; The North American Menopause Society (NAMS), 19th Annual Meeting.; 2008

The North American Menopause Society (NAMS)

Objective: Reorganization of the actin cytoskeleton via actin polymerization and depolymerization is required for various cellular processes, including control of cell morphology, adhesion and motility in various cell types, including brain cells. Estradiol (E2) controls the actin cytoskeleton via rapid signaling through estrogen receptors (ERs). WAVE-1, a member of the WASP (Wiskott-Aldrich syndrome protein) family of actin-regulatory proteins, controls thee branching of actin fibers in collaboration with the Arp 2/3 complex, thus promoting actin polymerization, membrane ruffling and the formation of lamellipodia. Design: To establish whether E2 may regulate neuronal morphology and branching via the actin cytoskeleton, we cultured fetal neuronal cells extracted from rats and we tested the molecular signaling of E2 to the actin-regulatory protein, WAVE-1. Results: We here find that E2 treatment of rat fetal neuronal cells leads to WAVE-1 phosphorylation, which is mediated by ER alpha. This phenomenon depends on a G protein/c-Src/Rac 1/cdk5 cascade. When activated, WAVE-1 is re-distributed along the leading edge of neuronal cells, leading to a reorganization of the actin cytoskeleton and the branching of axonal structures. Conclusions: In conclusion, our findings suggest that E2 plays an important role in the formation and extension of specialized membrane structures finked to membrane adhesion and cell-cell signaling in neural cells via the activation of WAVE-1. This study, establishes the signaling to the actin cytoskeleton through WAVE-1 as an important target of estrogens fur the functional control of neuronal cells.