Contributions of chaperone and glycosyltransferase activities of O-fucosyltransferase 1 to Notch signaling

BMC Biol. 2008 Jan 14;6:1. doi: 10.1186/1741-7007-6-1.

Abstract

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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Fucosyltransferases / genetics
  • Fucosyltransferases / metabolism*
  • Glycosyltransferases / genetics
  • Glycosyltransferases / metabolism*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Receptors, Notch / physiology
  • Signal Transduction / genetics
  • Signal Transduction / physiology*

Substances

  • Drosophila Proteins
  • Isoenzymes
  • Molecular Chaperones
  • Receptors, Notch
  • Glycosyltransferases
  • Fucosyltransferases
  • O-fucosyltransferase 1, Drosophila