We report here a PDZ dependent and protein kinase C modulated association between ASIC 3 and the Na+ / H+ exchanger regulatory factor 1 ( NHERF 1 ) adaptor protein . ^^^ We show that NHERF 1 and ASIC 3 are co expressed in dorsal root ganglion neurons . ^^^ NHERF 1 enhances the ASIC 3 peak current in heterologous cells , including F 11 dorsal root ganglion cells , by increasing the amount of channel at the plasma membrane . ^^^ Perhaps more importantly , we show that the plateau current of ASIC 3 can be dramatically increased ( 10 30 fold ) by association with NHERF 1 , leading to a significant sustained current at pH 6 . 6 . ^^^ In the presence of NHERF 1 , the ASIC 3 subcellular localization is modified , and the channel co localizes with ezrin , a member of the ezrin radixin moesin family of actin binding proteins , providing the first direct link between ASIC 3 and the cortical cytoskeleton . ^^^ |