Direct binding of the Na-H exchanger NHE1 to ERM proteins regulates the cortical cytoskeleton and cell shape independently of H+ translocation

The association of actin filaments with the plasma membrane maintains cell shape and adhesion. Here, we show that the plasma membrane ion exchanger NH E1 acts as an anchor for actin filaments to control the integrity of the co rtical cytoskeleton. This occurs through a previously unrecognized structur al link between NHE1 and the actin binding proteins ezrin, radixin, and moe sin (ERM). NHE1 and ERM proteins associate directly and colocalize in lamel lipodia. Fibroblasts expressing NHE1 with mutations that disrupt ERM bindin g, but not ion translocation, have impaired organization of focal adhesions and actin stress fibers, and an irregular cell shape. We propose a structu ral role for NHE1 in regulating the cortical cytoskeleton that is independe nt of its function as an ion exchanger.