title: neurotic, a novel maternal neurogenic gene, encodes an O-fucosyltransferase that is essential for Notch-Delta interactions.
abstract: Notch signalling, which is highly conserved from nematodes to mammals, plays crucial roles in many developmental processes. In the Drosophila embryo, deficiency in Notch signalling results in neural hyperplasia, commonly referred to as the neurogenic phenotype. We identify a novel maternal neurogenic gene, neurotic, and show that it is essential for Notch signalling. neurotic encodes a Drosophila homolog of mammalian GDP-fucose protein O-fucosyltransferase, which adds fucose sugar to epidermal growth factor-like repeats and is known to play a crucial role in Notch signalling. neurotic functions in a cell-autonomous manner, and genetic epistasis tests reveal that Neurotic is required for the activity of the full-length but not an activated form of Notch. Further, we show that neurotic is required for Fringe activity, which encodes a fucose-specific beta1, 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 the ability of Fringe to modulate this interaction in Drosophila cultured cells. We present an unprecedented example of an absolute requirement of a protein glycosylation event for a ligand-receptor interaction. Our results suggest that O-fucosylation catalysed 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.
authors.affiliation: PRESTO, Japan Science and Technology Corporation, Noda, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasamura
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sasaki
authors.forename: Fumiyasu
authors.initials: F
authors.lastname: Miyashita
authors.forename: Shiho
authors.initials: S
authors.lastname: Nakao
authors.forename: Hiroyuki O
authors.initials: HO
authors.lastname: Ishikawa
authors.forename: Mikiko
authors.initials: M
authors.lastname: Ito
authors.forename: Motoo
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harigaya
authors.forename: Eric
authors.initials: E
authors.lastname: Spana
authors.forename: David
authors.initials: D
authors.lastname: Bilder
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuno
mesh_terms: D000818:Animals; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins; D005647:Fucosyltransferases / Q000235:genetics* / Q000378:metabolism; D017930:Genes, Reporter; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D051880:Receptors, Notch
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C064045:delta protein; D005647:Fucosyltransferases