Notch ligand activity is modulated by glycosphingolipid membrane composition in Drosophila melanogaster.

ABSTRACT: Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors. The E3 ubiquitin ligases Mindbomb1 (Mib1) and Neuralized (Neur) regulate the ubiquitination of Dl and Ser and thereby promote both ligand endocytosis and Notch receptor activation. In this study, we identify the alpha1,4-N-acetylgalactosaminyltransferase-1 (alpha4GT1) gene as a gain of function suppressor of Mib1 inhibition. Expression of alpha4GT1 suppressed the signaling and endocytosis defects of Dl and Ser resulting from the inhibition of mib1 and/or neur activity. Genetic and biochemical evidence indicate that alpha4GT1 plays a regulatory but nonessential function in Notch signaling via the synthesis of a specific glycosphingolipid (GSL), N5, produced by alph

SUBMITTER: Hamel S 

PROVIDER: S-EPMC2828914 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature