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First published online 13 August 2003
doi: 10.1242/dev.00679
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1 PRESTO, Japan Science and Technology Corporation
2 Department of Biological Science and Technology, Tokyo University of Science,
Yamazaki 2641, Noda, Chiba 278-8510, Japan
3 Genome and Drug Research Center, Tokyo University of Science, Yamazaki 2641,
Noda, Chiba 278-8510, Japan
4 Department of Nutrition, School of Medicine, University of Tokushima, 3-18-15
Kuramoto, Tokushima 770-8503, Japan
5 Department of Molecular and Tumor Pathology, Chiba University Graduate School
of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
6 Department of Biology, Developmental, Cell and Molecular Biology Group, Duke
University, Durham, NC 27708, USA
7 Department of Genetics, Howard Hughes Medical Institute, Harvard Medical
School, 200 Longwood Avenue, Boston, MA 02115, USA
* Author for correspondence (e-mail: matsuno{at}rs.noda.tus.ac.jp)
Accepted 20 June 2003
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 ß1, 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.
Key words: Notch signalling, Neurogenic gene, neurotic, nti, O-fucosyltransferase, Fucose, Fringe, Notch-Delta binding, Drosophila
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