Ligand-receptor interactions and trans-endocytosis of Delta, Serrate and Notch: members of the Notch signalling pathway in Drosophila

Abstract

Molecular evidence has established that direct heterotypic interactions occur between the Drosophila receptor Notch and the ligands Delta and Serrate, and that homotypic interactions occur between Delta molecules on opposing cell surfaces. Using an aggregation assay developed for Drosophila cultured cells, we have compared the affinities of these interactions. We find that the heterotypic interactions between Notch and the ligands Delta and Serrate have higher affinities than homotypic interactions between Delta molecules. Contrary to previous suggestions, our evidence implies that the interactions between Serrate and Notch are similar in affinity to those between Delta and Notch. We find that Fringe does not detectably affect the ligand-receptor interactions of the Notch pathway in cultured cells. Furthermore, we find that Serrate, like Delta, is a transmembrane ligand that can participate in reciprocal trans-endocytosis of ligand and receptor between expressing cells. Our findings imply that qualitative differences between Delta- and Serrate-mediated Notch signalling depend on characteristics other than intrinsic ligand-receptor affinities or the ability to participate in reciprocal ligand and receptor trans-endocytosis.