NHE-RF, a Regulatory Cofactor for Na+-H+Exchange, Is a Common Interactor for Merlin and ERM (MERM) Proteins

• Published in: The Journal of biological chemistry Vol. 273; no. 3; pp. 1273 - 1276
• Main Authors: Murthy, Anita, Gonzalez-Agosti, Charo, Cordero, Etchell, Pinney, Denise, Candia, Cecilia, Solomon, Frank, Gusella, James, Ramesh, Vijaya
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16-01-1998; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Animals; Cloning, Molecular; COS Cells; Cyclic AMP-Dependent Protein Kinases - metabolism; DNA-Binding Proteins - metabolism; Genes, Neurofibromatosis 2; HeLa Cells; Humans; Immunoenzyme Techniques; Membrane Proteins - metabolism; Molecular Sequence Data; Neoplasm Proteins - metabolism; Neurofibromin 2; Phosphoproteins - genetics; Phosphoproteins - metabolism; Sodium-Hydrogen Exchanger 3; Sodium-Hydrogen Exchangers - metabolism; Transcription Factors - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.3.1273

We have identified the human homologue of a regulatory cofactor of Na+-H+ exchanger (NHE-RF) as a novel interactor for merlin, the neurofibromatosis 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, downstream of the PDZ domains, interacts with the amino-terminal protein 4.1 domain-containing segment of merlin in yeast two-hybrid assays. This interaction also occurs in affinity binding assays with full-length NHE-RF expressed in COS-7 cells. NHE-RF binds to the related ERM proteins, moesin and radixin. We have localized human NHE-RF to actin-rich structures such as membrane ruffles, microvilli, and filopodia in HeLa and COS-7 cells, where it co-localizes with merlin and moesin. These findings suggest that hNHE-RF and its binding partners may participate in a larger complex (one component of which might be a Na+-H+exchanger) that could be crucial for the actin filament assembly activated by the ERM proteins and for the tumor suppressor function of merlin.