Fringe gives a saccharine to notch

Post-translational modifications like phosphorylation, acetylation and fatty acid acylation of proteins are well-known strategies that cells use to regulate the activity of enzymes and maintain the binding properties of ligands and receptors. By contrast, glycosylation, where carbohydrates are attached to the side chains of amino acids, is important in the synthesis of many secreted and cell-surface proteins. Moloney et al.1 and Brückner et al.2 now demonstrate that elongation of O-linked fucose on glycosylated proteins can act as an as-yet-unknown post-translational regulatory mechanism for modulating receptor–ligand interactions in signal transduction. Both groups studied the influence of glycosylation on the activity of Notch-induced signalling, which is important for the formation of tissue boundaries during development. Notch receptors are transmembrane proteins with an extracellular domain of epidermal growth factor (EGF)-like repeats and are activated by two conserved families of ligand proteins, Jagged/Serrate and Delta. Molony et al. show that Fringe, a modulator of Notch, possess a fucosespecific glycosyltransferase activity that catalyses the elongation of carbohydrates on the EGF repeats of the receptor protein. Using tritium-labelled saccharides they found that EGF–Ofucose is a highly specific target for Fringe. The elongation of the glycans on Notch led to an inhibitory effect on the activation of its ligand, Jagged1, as monitored by a luciferase-reporter assay. Brückner et al. demonstrate that Fringe displays its ability to modify Notch within the Golgi apparatus and that modulation of the receptor increases the binding activity to its ligand Delta. Both groups show that the Notch–ligand interaction is not affected when replacing the DxD motif (aa 236–238) in Fringe, required for the catalytic activity in many glycosyltransferases, by either NNN or DEE. Condensing the RNA world