Presenilin suppresses the negative complementation at the Notch locus of Drosophila melanogaster, suggesting a mechanism for negative complementation

Abstract

A loss-of-function mutant form of the Presenilin (Psn) gene from the third chromosome, known to be involved in the proteolytic cleavage of the Notch receptor protein on the cell membrane of Drosophila melanogaster and the access of its intracellular domain to the nucleus, completely rescues the lethality caused by the negative complementation in certain heteroallelic combinations of the Abruptex (Ax) type mutations of the Notch locus in the X chromosome. On the other hand, Presenilin enhances the negative complementation of one particular semilethal Abruptex genotype (Ax28/AxE2). Since the Abruptex mutations are point mutations of the extracellular domain of the Notch receptor located close to the binding site of the Delta ligand, it is suggested that the mechanism of negative complementation at the Notch locus is the impairment of the ligand activation of the Notch receptor, subsequently followed by the failure of the cleavage of the receptor protein and impairment of the access of the intracellular domain into the nucleus.