Effect of Knockdown of Ezrin, Radixin, and Moesin on P-Glycoprotein Function in HepG2 Cells

Ezrin, radixin, and moesin (ERM) proteins regulate functional expression of certain transporters, but little is known about their effect on P‐glycoprotein (P‐gp). Here, we investigated the influence of ERM proteins on the expression and activity of P‐gp at the transcriptional, translational, and posttranslational levels, using HepG2 as a model cell line. Knockdown of ezrin with RNA interference decreased the level of P‐gp messenger RNA. On the contrary, knockdown of radixin caused a decrease of the P‐gp gene product at the cell surface, but not in whole cell lysate. Furthermore, a significant increase in accumulation of rhodamine123, a typical P‐gp substrate, was observed in radixin knockdown cells, compared with control cells. Knockdown of moesin did not influence the expression or function of P‐gp. These results indicate that ezrin influences the expression of P‐gp at the translational level, whereas radixin is involved in membrane localization of P‐gp in HepG2 cells.