초록 열기/닫기 버튼
Glutamate induced rapid phosphorylation of moe-sin, one of ERM family proteins involved in the ligation of membrane to actin cytoskeleton, in rat hipocampal cells (JBC, 277:16576-16584, 2002). However, the identity of glutamate receptor has not been explored. Here we show that a-amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is responsible for glutamate-induced RhoA activation and phosphorylation of moesin. Gluta-mate induced phosphorylation at Thr-58 of moe-sin was stil detectible upon chelation of Ca2+, sugesting involvement of AMPA receptor instead of N-methyl D-Aspartate (NMDA) receptor in this phosphorylation of moesin. AMPA but not NMDA- induced moesin phosphorylation was indepen-dent of Ca2+. Both AMPA and NMDA but not levels. However, the kinetics of phosphorylation varied greatly between AMPA and NMDA where AMPA treatment rapidly increased phosphomoe-sin, which reached a maximum at 10 min after treatment and returned to a basal level at 30 min. In contrast, NMDA-induced phosphorylation of moesin reached a maximum at 30 min after treatment and was remained at higher levels at 60 min. A possible involvement of RhoA and its downstream effector, Rho kinase in the AMPA receptor-trigered phosphorylation of moesin was also explored. The kinetics for the glutamate- in-duced membrane translocation of RhoA was simi-lar to that of moesin phosphorylation induced by AMPA. Moreover, Y-27632, a specific Rho kinase inhibitor, completely blocked AMPA-induced moesin phosphorylation but had no efect on NMDA-in-duced moesin phosphorylation. These results sug-gest that glutamate-induced phosphorylation of moesin may be mediated through the AMPA receptor/RhoA/Rho kinase pathway.
키워드열기/닫기 버튼
AMPA; Moesin; NMDA; Rho GTPase; ROK; phsophorylation
