Overexpression Of Tau Regulated The MRNA Levels Of Kv Channels And Proliferation In Cells

Microtubule binding protein tau has a crucial function in promoting the assembly and stabilization of microtubule and the proliferation rates of cells.Besides tuning the action potentials,voltage-gated K~+channels(Kv)are important for cell proliferation and appear to play a role in the development of cancer.However,little is known about the possible interaction of tau with Kv channels in various tissues.The aim of this study is exploration between the two in vitro and its relationship with cell proliferation.In the present study,tau plasmids were transiently transfected into mouse neuroblastoma N2A cells and human neuroblastoma SK-N-SH cells to explore the possible linkages between tau and Kv channels.Treatment led to a downregulation of mRNA levels of several Kv channels,including Kv2.1,Kv3.1,Kv4.1,Kv9.2,and KCNH4,but no significant alteration was observed for Kv5.1 and KCNQ4 in N2A cells.A significant reduction in the mRNA levels of Kv2.1,Kv3.1,Kv5.1,Kv9.2,and KCNH4 was detected in SK-N-SH cells.Furthermore,the macroscopic currents through Kv channels were reduced at+60 mV in tau-tranfected N2A and SK-N-SH cells.The proliferation rates of cells were also improved,such as the N2A cells by the induction of tau expression and the incubation of TEA(tetraethylammonium)for 48h by 120.9%and 149.3%,respectively.Following the cotransfection with tau in HEK293 cells,the mRNA levels and corresponding currents of Kv2.1 were significantly declined compared with single Kv2.1 transfection.Similar phenomena were found in SK-N-SH cells.Our study suggests that the effects of tau overexpression on Kv channels provided an alternative explanation for low sensitivity to anticancer chemicals in some specific cancer tissues.