Apical-basal polarity is essential for the function and integrity of epithelia and mediated by a number of polarity proteins, including Scribble. Cell polarisation also requires spatially restricted cytoskeleton remodelling; this is mediated by the Rho family of small GTPases and their GTPase-activating proteins, the RhoGAPs. Deleted in liver cancer 3 (DLC3) is a poorly characterised RhoGAP that has been found at cell–cell contacts and, in this study (p. 3583), Monilola Olayioye and co-workers performed mass spectrometry analysis to identify Scribble as a binding partner of DLC3. They show here that Scribble and DLC3 depend on each other for localisation to cell–cell junctions, and define the regions that are involved: the PDZ domains in Scribble and a PDZL motif in DLC3. By using a RhoA biosensor and a targeted GAP domain, the authors then demonstrate that RhoA activity at cell–cell junctions and junctional integrity are regulated through DLC3 and mediated by concomitant localisation of Scribble to the junction. Furthermore, knockdown of DLC3 and Scribble in a 3D model of cyst formation results in impaired morphogenesis with failure of cells to form a lumen, emphasising the relevance of both proteins in the establishment of polarity. On the basis of these findings, the authors propose a new function for Scribble in Rho regulation that involves positioning the GAP activity of DLC3 at cell–cell junctions in epithelial polarised cells.
- © 2016. Published by The Company of Biologists Ltd