Moesin functions antagonistically to the Rho pathway to maintain epithelial integrity.
Two prominent characteristics of epithelial cells, apical-basal polarity and a highly ordered cytoskeleton, depend on the existence of precisely localized protein complexes associated with the apical plasma membrane, and on a separate machinery that regulates the spatial order of actin assembly. ERM (ezrin, radixin, moesin) proteins have been proposed to link transmembrane proteins to the actin cytoskeleton in the apical domain, suggesting a structural role in epithelial cells, and they have been implicated in signalling pathways. Here, we show that the sole Drosophila ERM protein Moesin functions to promote cortical actin assembly and apical-basal polarity. As a result, cells lacking Moesin lose epithelial characteristics and adopt invasive migratory behaviour. Our data demonstrate that Moesin facilitates epithelial morphology not by providing an essential structural function, but rather by antagonizing activity of the small GTPase Rho. Thus, Moesin functions in maintaining epithelial integrity by regulating cell-signalling events that affect actin organization and polarity. Furthermore, our results show that there is negative feedback between ERM activation and activity of the Rho pathway.
Speck
Olga
O
DCMB Group, Department of Biology, Duke University, Box 91000, Durham, North Carolina 27708, USA.
Hughes
Sarah C
SC
Noren
Nicole K
NK
Kulikauskas
Rima M
RM
Fehon
Richard G
RG
D000199:Actins / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D002465:Cell Movement; D016764:Cell Polarity; D048429:Cell Size; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D025461:Feedback, Physiological; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099149:Ezrin
D000199:Actins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D020741:rho GTP-Binding Proteins; D000099149:Ezrin; C071058:moesin; C511153:Rho1 protein, Drosophila