Epithelial polarity and architecture rely on the asymmetric positioning of evolutionarily conserved polarity proteins. Lethal Giant Larvae (Lgl) is one such protein: it localizes to the lateral cortex of cells and acts together with Scribble (Scrib) and Discs Large (Dlg) to promote basolateral identity. Although these basolateral determinants are known to antagonise the activity of apical polarity proteins, such as aPKC, their precise mechanism of action – and whether they function together in a complex – has remained unclear. Here, Eurico Morais-de-Sá and colleagues investigate this issue using the Drosophila follicular epithelium as a model. They first report that Lgl is significantly more dynamic than Scrib and Dlg, as detected by fluorescence recovery after photobleaching experiments. Using optogenetic depletion of PIP2, they further show that Lgl dynamics rely on PIP2 but are independent of aPKC in the lateral cortex and do not require protein-protein interactions with Scrib-Dlg. Finally, in line with these findings, the researchers demonstrate that Scrib-Dlg complexes detected in vivo do not contain Lgl. Overall, these studies indicate that Lgl does not act in a complex with Scrib-Dlg, but instead acts in parallel with these factors to antagonize apical determinants.

© 2020. Published by The Company of Biologists Ltd
2020