NHE-RF, A REGULATORY COFACTOR FOR NA-H+ EXCHANGE, IS A COMMON INTERACTOR FOR MERLIN AND ERM (MERM) PROTEINS()

We have identified the human homologue of a regulatory cofactor of Na-H+ exchanger (NHE-RF) as a novel interactor for merlin, the neurofibr omatosis 2 tumor suppressor protein, NHE-RF mediates protein kinase A regulation of Na+-H+ exchanger NHE3 to which it is thought to bind via one of its two PDZ domains. The carboxyl-terminal region of NHE-RF, d ownstream of the PDZ domains, interacts with the amino-terminal protei n 4.1 domain-containing segment of merlin in yeast two-hybrid assays. This interaction also occurs in affinity binding assays with full-leng th NHE-RF expressed in COS-7 cells. NHE-RF binds to the related ERM pr oteins, moesin and radixin. We have localized human NHE-RF to actin-ri ch structures such as membrane ruffles, microvilli, and filopodia in H eLa and COS-7 cells, where it co-localizes with merlin and moesin, The se findings suggest that hNHE-RF and its binding partners may particip ate in a larger complex (one component of which might be a Na+-H+ exch anger) that could be crucial for the actin filament assembly activated by the ERM proteins and for the tumor suppressor function of merlin.