Contributions of chaperone and glycosyltransferase activities of O-fucosyltransferase 1 to Notch signaling.
BACKGROUND
O-fucosyltransferase1 (OFUT1) is a conserved ER protein essential for Notch signaling. OFUT1 glycosylates EGF domains, which can then be further modified by the N-acetylglucosaminyltransferase Fringe. OFUT1 also possesses a chaperone activity that promotes the folding and secretion of Notch. Here, we investigate the respective contributions of these activities to Notch signaling in Drosophila.


RESULTS
We show that expression of an isoform lacking fucosyltransferase activity, Ofut1R245A, rescues the requirement for Ofut1 in embryonic neurogenesis. Lack of requirement for O-fucosylation is further supported by the absence of embryonic phenotypes in Gmd mutants, which lack all forms of fucosylation. Requirements for O-fucose during imaginal development were evaluated by characterizing clones of cells expressing only Ofut1R245A. These clones phenocopy fringe mutant clones, indicating that the absence of O-fucose is functionally equivalent to the absence of elongated O-fucose.


CONCLUSIONS
Our results establish that Notch does not need to be O-fucosylated for fringe-independent Notch signaling in Drosophila; the chaperone activity of OFUT1 is sufficient for the generation of functional Notch.
Okajima
Tetsuya
T
Nagoya University Graduate School of Bioagricultural Sciences, Department of Applied Molecular Biosciences, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. tokajima@agr.nagoya-u.ac.jp
Reddy
Bvvg
B
Matsuda
Tsukasa
T
Irvine
Kenneth D
KD
D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
D029721:Drosophila Proteins; D007527:Isoenzymes; D018832:Molecular Chaperones; D051880:Receptors, Notch; D016695:Glycosyltransferases; D005647:Fucosyltransferases; C471275:O-fucosyltransferase 1, Drosophila