Moesin functions antagonistically to the Rho pathway to maintain epithelial integrity

Abstract

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 membrane1,2, and on a separate machinery that regulates the spatial order of actin assembly3. ERM (ezrin, radixin, moesin) proteins have been proposed to link transmembrane proteins to the actin cytoskeleton4 in the apical domain, suggesting a structural role in epithelial cells, and they have been implicated in signalling pathways5. 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.

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Figure 1: Moesin and Rho1 control filamentous actin.
Figure 2: Loss of Moesin and overexpression of Rho1 cause loss of apical-basal polarity.
Figure 3: Loss of Moesin and overexpression of Rho1 induce invasive migratory cellular behaviour.
Figure 4: ERM proteins negatively regulate Rho pathway activity in epithelial cells.

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Acknowledgements

We are grateful to K. Burridge for providing resources for the Rho activation assay; K. Johnson for sharing bench space and expertise; T. Jacks, in whose laboratory the work with mouse ERMs was begun during a sabbatical leave; J. Genova for advice on electron microscopy, and D. Kiehart, D. Lew, I. Rebay, J. Genova and S. Maitra for comments on the manuscript. We would also like to thank H. Gavilan for valuable technical assistance. This work was supported by National Institutes of Health grants to R.G.F. and to K. Burridge.

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Correspondence to Richard G. Fehon.

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Speck, O., Hughes, S., Noren, N. et al. Moesin functions antagonistically to the Rho pathway to maintain epithelial integrity. Nature 421, 83–87 (2003). https://doi.org/10.1038/nature01295

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