Regulation of notch signaling by o-linked fucose.
Notch and its ligands are modified by a protein O-fucosyltransferase (OFUT1) that attaches fucose to a Serine or Threonine within EGF domains. By using RNAi to decrease Ofut1 expression in Drosophila, we demonstrate that O-linked fucose is positively required for Notch signaling, including both Fringe-dependent and Fringe-independent processes. The requirement for Ofut1 is cell autonomous, in the signal-receiving cell, and upstream of Notch activation. The transcription of Ofut1 is developmentally regulated, and surprisingly, overexpression of Ofut1 inhibits Notch signaling. Together, these results indicate that OFUT1 is a core component of the Notch pathway, which is required for the activation of Notch by its ligands, and whose regulation may contribute to the pattern of Notch activation during development.
Okajima
Tetsuya
T
Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Irvine
Kenneth D
KD
D000818:Animals; D016466:CHO Cells; D019070:Cell Lineage; D003001:Cloning, Molecular; D006224:Cricetinae; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008957:Models, Genetic; D010641:Phenotype; D034622:RNA Interference; D051880:Receptors, Notch; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014018:Tissue Distribution; D014921:Wings, Animal / Q000196:embryology
D029721:Drosophila Proteins; D008024:Ligands; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D005643:Fucose; D005647:Fucosyltransferases; C471275:O-fucosyltransferase 1, Drosophila