title: ERM proteins mediate the effects of Na+/H+ exchanger (NHE1) activation in cardiac myocytes.
abstract: OBJECTIVE
  Ezrin, radixin, and moesin (ERM) proteins have been implicated in regulating signalling molecules. The aim of the present study was to investigate the activity and subcellular distribution of ERM proteins in cardiac myocytes from both Wistar and diabetic Goto-Kakizaki (GK) rats, and the role of these proteins in mediating the downstream effects of the cardiac sarcolemmal Na+/H+ exchanger (NHE1) activation in response to cell acidification.
  
  
  RESULTS
  Immunofluorescence microscopy revealed that activated ERM proteins were localized predominantly at the intercalated disc regions in left ventricular (LV) myocytes of both Wistar and GK rats under basal conditions. After acid loading, profound changes in activated ERM distribution were observed in both groups of myocytes, with immunolabelling detected in regions corresponding to the transverse tubules. This correlated with a marked increase in phospho-ERM levels in both groups, which was higher in GK myocytes and blocked by NHE1 inhibitor treatment. Levels of phospho-Akt paralleled those of phospho-ERM under the various experimental conditions used; in particular, the marked acid-induced increase in both phospho-ERM and phospho-Akt in GK myocytes was abolished by an NHE1 inhibitor treatment. Moreover, the pattern of glycogen synthase kinase-3beta (GSK-3beta) phosphorylation in these myocytes was strikingly similar to that observed for Akt activity under the conditions used.
  
  
  CONCLUSIONS
  Activated ERM proteins mediate the effects of acid-induced NHE1 activation in LV myocytes. Akt is a downstream effector in the cascade activated by NHE1-ERM interaction. In addition, GSK-3beta phosphorylation is required for downstream effects of NHE1/ERM-Akt signalling.
authors.affiliation: University of Paris-Sud 11 and CNRS UMR 8162, Marie Lannelongue Hospital, 133 avenue de la Résistance, 92350 Le Plessis Robinson, France.
authors.forename: Amaria
authors.initials: A
authors.lastname: Darmellah
authors.forename: Catherine
authors.initials: C
authors.lastname: Rücker-Martin
authors.forename: Danielle
authors.initials: D
authors.lastname: Feuvray
mesh_terms: D000818:Animals; D003598:Cytoskeletal Proteins / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D008840:Microfilament Proteins / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology; D015398:Signal Transduction; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D054460:rho-Associated Kinases / Q000502:physiology; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D008565:Membrane Proteins; D008840:Microfilament Proteins; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D058570:TOR Serine-Threonine Kinases; D054460:rho-Associated Kinases; D000099149:Ezrin; C452850:Slc9a1 protein, rat; C071058:moesin; C071776:radixin; C546845:mTOR protein, rat; C000605508:Gsk3b protein, rat