| Research Abstract |
Notch signalling, which is highly conserved from nematodes to mammals, plays critical roles in many developmental processes.In the Drosophila embryo, deficiency in Notch signalling results in neurohyperplasia, commonly referred to as the neurogenic phenotype.Here we identify a novel maternal neurogenic gene, neurotic, and show that it is essential for Notch signalling, neurotic encodes a protein highly homologous to mammalian GDP-fucose protein O-fucosyltransferase, which adds fucose sugar to epidermal growth factor-like repeats.neurotic functions in a cell autonomous manner, and genetic epistasis tests reveal that Neurotic is required for the activity of full-length but not an activated form of Notch.Further, we show that neurotic is required for Fringe activity, which encodes a fucose-specific,β1,3 N-acetylglucosaminyltransferase, previously shown to modulate Notch receptor activity.Finally, Neurotic is essential for the physical interaction of Notch with its ligand Delta, and for Fringe ability to modulate this interaction in Drosophila cultured cells.We present here an unprecedented example of an absolute requirement of a protein glycosylation event for a ligand-receptor interaction.Our results suggest,that O-fucosylation catalyzed by Neurotic is also involved in the Fringe-independent activities of Notch and may provide a novel on-off mechanism that regulates ligand-receptor interactions.
|
