title: Sip1, the Drosophila orthologue of EBP50/NHERF1, functions with the sterile 20 family kinase Slik to regulate Moesin activity.
abstract: Organization of the plasma membrane in polarized epithelial cells is accomplished by the specific localization of transmembrane or membrane-associated proteins, which are often linked to cytoplasmic protein complexes, including the actin cytoskeleton. In this study, we identified Sip1 as a Drosophila orthologue of the ezrin-radixin-moesin (ERM) binding protein 50 (EBP50; also known as the Na(+)/H(+) exchanger regulatory factor NHERF1). In mammals, EBP50/NHERF1 is a scaffold protein required for the regulation of several transmembrane receptors and downstream signal transduction activity. In Drosophila, loss of Sip1 leads to a reduction in Slik kinase protein abundance, loss of Moesin phosphorylation and changes in epithelial structure, including mislocalization of E-cadherin and F-actin. Consistent with these findings, Moesin and Sip1 act synergistically in genetic-interaction experiments, and Sip1 protein abundance is dependent on Moesin. Co-immunoprecipitation experiments indicate that Sip1 forms a complex with both Moesin and Slik. Taken together, these data suggest that Sip1 promotes Slik-dependent phosphorylation of Moesin, and suggests a mechanism for the regulation of Moesin activity within the cell to maintain epithelial integrity.
authors.affiliation: Department of Medical Genetics, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada. sarah.hughes@ualberta.ca
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Hughes
authors.forename: Etienne
authors.initials: E
authors.lastname: Formstecher
authors.forename: Richard G
authors.initials: RG
authors.lastname: Fehon
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D058112:Septins; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics
chemical_list: D000199:Actins; D015820:Cadherins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C099886:moesin, Drosophila; C093376:sodium-hydrogen exchanger regulatory factor; D017346:Protein Serine-Threonine Kinases; C492662:Slik protein, Drosophila; D020558:GTP Phosphohydrolases; C522167:Sep1 protein, Drosophila; D058112:Septins