Abstract
BackgroundO-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.ResultsWe 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.ConclusionOur 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.
Highlights
O-fucosyltransferase1 (OFUT1) is a conserved ER protein essential for Notch signaling
The fact that OFUT1 possesses both fucosyltransferase and chaperone activity for Notch raises the question of the respective contributions of these two activities to the genetic requirement for OFUT1 in Notch signaling. We have addressed this by examining the in vivo activity of Notch produced in cells with OFUT1 chaperone activity, but lacking fucosyltransferase activity
O-fucosylation of Notch is not required during embryonic neurogenesis We have taken two complementary approaches to evaluate the respective contributions of the fucosyltransferase and chaperone activities of OFUT1 to Notch signaling
Summary
O-fucosyltransferase (OFUT1) is a conserved ER protein essential for Notch signaling. Notch signaling is influenced by two conserved glycosyltransferases, O-fucosyltransferase (OFUT1) and Fringe (FNG) [2]. Fringe was first identified because of its role in modulating Notch signaling during the development of the Drosophila wing, where it both potentiates the activation of Notch by one ligand, Delta, and inhibits the activation of Notch by another ligand, Serrate [5]. These opposing effects of Fringe on the activation of Notch by its ligands, together with the restriction of normal Fringe expression to dorsal wing cells, help to position a stripe of Notch acti-
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