The polarity protein Yurt associates with the lateral domain via basic and hydrophobic motifs embedded in its FERM domain

Abstract

AbstractThe subcellular distribution of the polarity protein Yrt is subjected to a spatio-temporal regulation inD. melanogasterembryonic epithelia. After cellularization, Yrt binds to the lateral membrane of ectodermal cells and maintains this localization throughout embryogenesis. During terminal differentiation of the epidermis, Yrt accumulates to septate junctions and is also recruited to the apical domain. While the mechanisms through which Yrt associates with septate junctions and the apical domain have been deciphered, how Yrt binds to the lateral membrane remains as an outstanding puzzle. Here, using anin vivostructure-function analysis, we show that the FERM domain of Yrt is necessary and sufficient for lateral localization. Our data also establish that the FERM domain of Yrt directly binds negatively charged phospholipids. Moreover, we demonstrate that positively charged amino acid motifs embedded within the FERM domain mediates Yrt membrane association. Finally, we provide evidence suggesting that Yrt association with the lateral membrane is functionally important. Overall, our study highlights the molecular basis of how Yrt associates with the lateral membrane before septate junction formation, a developmental time window where Yrt is required for segregation of lateral and apical domains. Our discoveries could thus contribute to further understanding of how epithelial cells acquire their polarized architecture.