Effect of estradiol on actin cytoskeleton in neural cells via WAVE-1.

A.M. SANCHEZ; M. FLAMINI; X.D. FU; S. GARIBALDI; M.S. GIRETTI; P. MANNELLA; C. BALDACCI; L. GOGLIA; S. PISANESCHI; A. CARUSO; A.R. GENAZZANI; T. SIMONCINI

8-11 March, Rome, Italy

Congreso; The 2nd World Congress on Gender-Specific Medicine and Ageing. The Endocrine Impact.; 2007

Actin dynamics plays a central role in cellular function. Reorganization of the actin cytoskeleton, via actin polymerization and depolymerization, is required for vary cellular processes, including cell morphology, cell adhesion and motility. These processes are regulated by sex steroid hormones, such as Estradiol (E2). Our previous findings have shown that E2 induces rapid cytoskeletal and cell membrane remodeling. It is as well established that actin cytoskeleton remodeling is regulated by WAVE, one member of the WASP (Wiskott- Aldrich syndrome protein) family, by relaying signals from Rho/Rac GTPases to the Arp2/3 complex that promotes the formation and branching of actin filaments. WAVE proteins also play key roles in the induction of various actin remodeling processes including membrane ruffling and lamellipodia formation. In neural cells, WAVE-1 protein is phosphorylated at multiple sites and this is need to regulate Arp2/3 complex-dependent actin polymerization, essential for lamellipodia protrusion. However it remains unclear whether the action of E2 on actin cytoskeleton remodelling is mediated by WAVE. For this reason, we have studied effects of estrogen on WAVE-1 activation in SK-N-SH neuroblastoma cells. Our results showed that WAVE-1 is activated in the presence of E2. Afterwards, WAVE-1 is distributed along the leading edge, converting the signals of E2 to the reorganization of the actin cytoskeleton. In conclusion, our findings suggest E2 plays an important role in the formation and extension of lamellipodial via the activation of WAVE-1. Further efforts will be required to this field to expand our understanding on actin dynamics and cell remodeling in neural cells.