Apical-basal polarity is crucial for epithelial function, and is established and maintained by conserved polarity proteins, many of which also act as tumour suppressors. Correctly targeting these proteins to the plasma membrane (PM) is crucial for their function, but the control of this targeting remains incompletely understood. Recent work has implicated ‘polybasic domains’, highly positively charged regions of 20-40 amino acids that electrostatically bind the PM, in targeting of some polarity proteins. Now Yang Hong and colleagues show that this is also the case for another, Discs large (Dlg), in Drosophila. They first identify the Dlg polybasic domain, which spans the previously known SH3 and HOOK domains. Swapping positively charged for neutral residues in this domain leads to a failure of Dlg PM localisation in epithelia. By depleting PMs of negatively charged phospholipids such as PI4P and PIP2, the authors show that electrostatic PM binding contributes significantly to Dlg targeting; PDZ domains and septate junctions provide alternate, redundant routes. Dlg targeting is potentially controlled by phosphorylation-dependent allosteric regulation of the polybasic domain, and is enhanced by the polarity protein Scrib; a milder effect is seen with Lgl. Finally, electrostatic PM targeting is essential for Dlg to regulate apical-basal polarity and act as a tumour suppressor. This work thus adds Dlg to the polybasic polarity protein family.
Stay positive: a polybasic domain helps Dlg get to the plasma membrane
Stay positive: a polybasic domain helps Dlg get to the plasma membrane. Development 1 April 2021; 148 (7): e148_e0701. doi:
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