Reference Report

Reference
Citation	Lei, L., Xu, A., Panin, V.M., Irvine, K.D. (2003). An O-fucose site in the ligand binding domain inhibits Notch activation. Development 130(26): 6411--6421. (Export to RIS)
FlyBase ID	FBrf0167520
Publication Type	Research paper
PubMed ID	14627724
PubMed Abstract	Two glycosyltransferases that transfer sugars to EGF domains, OFUT1 and Fringe, regulate Notch signaling. However, sites of O-fucosylation on Notch that influence Notch activation have not been previously identified. Moreover, the influences of OFUT1 and Fringe on Notch activation can be positive or negative, depending on their levels of expression and on whether Delta or Serrate is signaling to Notch. Here, we describe the consequences of eliminating individual, highly conserved sites of O-fucose attachment to Notch. Our results indicate that glycosylation of an EGF domain proposed to be essential for ligand binding, EGF12, is crucial to the inhibition of Serrate-to-Notch signaling by Fringe. Expression of an EGF12 mutant of Notch (N-EGF12f) allows Notch activation by Serrate even in the presence of Fringe. By contrast, elimination of three other highly conserved sites of O-fucosylation does not have detectable effects. Binding assays with a soluble Notch extracellular domain fusion protein and ligand-expressing cells indicate that the NEGF12f mutation can influence Notch activation by preventing Fringe from blocking Notch-Serrate binding. The N-EGF12f mutant can substitute for endogenous Notch during embryonic neurogenesis, but not at the dorsoventral boundary of the wing. Thus, inhibition of Notch-Serrate binding by O-fucosylation of EGF12 might be needed in certain contexts to allow efficient Notch signaling.
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Language of Publication	English
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Parent Publication
Publication Type	Journal
Abbreviation	Development
Title	Development
Publication Year	1987-
ISBN/ISSN	0950-1991
Data from Reference
Alleles (21)
	Avic\GFP^{S65T.Scer\UAS} Dl^RevF10 Ecol\lacZ^Scer\UAS.cBa fng^Scer\UAS.cKa N^55e11 N^865.Scer\UAS N^{EGF12f.MtnA.T:Hsap\ALPP} N^EGF12f.MtnA N^{EGF12f.Scer\UAS} N^{EGF24f.Scer\UAS} N^{EGF26f.Scer\UAS} N^{EGF31f.Scer\UAS} N^{EGF.10-12.MtnA.Bip.T:SV5\V5,T:Zzzz\His6} N^{EGF.10-12f.MtnA.Bip.T:SV5\V5,T:Zzzz\His6} N^{MtnA.T:Hsap\ALPP} Scer\GAL4^da.G32 Scer\GAL4^ptc-559.1 Scer\GAL4^{Scer\FRT.Act5C} Scer\GAL4^αTub84B.PL Scer\GAL80^αTub84B.PL Ser^rev2-11
Constructs (12)
	P{AyGAL4} P{GAL4-da.G32} P{tubP-GAL4} P{tubP-GAL80} P{UAS-fng.K} P{UAS-GFP.S65T} P{UAS-lacZ.B} P{UAS-N.865} P{UAS-N.S502A} P{UAS-N.S1036A} P{UAS-N.T960V} P{UAS-N.T1235V}
Genes (15)
	Avic\GFP Dl Ecol\lacZ elav fng N O-fut1 Scer\GAL4 Scer\GAL80 Ser Sxl T:Hsap\ALPP T:SV5\V5 T:Zzzz\His6 wg
Insertions (2)
	P{GawB}ptc^559.1 P{UAS-fng.K}27
Natural transposons (1)
	P-element