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

Quebec, Canada

Congreso; 13th International Congress on Hormonal Steroids and Hormones & Cancer.; 2008

Actin dynamics plays a central role in cellular function. Reorganization of the actin cytoskeleton, via actin polymerization and depolymerization, is required for various 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 toward 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 Rac1 GTPases, to cyclin-dependent kinase Cdk5 interactively with the WAVE-1 complex, that regulate directly binds to the Arp2/3 complex, mediate the actin polymerization process. WAVE proteins 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 for cdk5 and this is need to regulate Arp2/3 complex-dependent actin polymerization, essential for lamellipodia protrusion. Our results showed that E2 led to WAVE-1 phosphorylation, which was mediated by ER alpha and the recruitment of signalings including G protein/c-Src/Rac1/cdk5 cascade. When activated, WAVE-1 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 lamellipodium 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.