Reference Report

Reference
Citation	Sasamura, T., Ishikawa, H.O., Sasaki, N., Higashi, S., Kanai, M., Nakao, S., Ayukawa, T., Aigaki, T., Noda, K., Miyoshi, E., Taniguchi, N., Matsuno, K. (2007). The O-fucosyltransferase O-fut1 is an extracellular component that is essential for the constitutive endocytic trafficking of Notch in Drosophila. Development 134(7): 1347--1356. (Export to RIS)
FlyBase ID	FBrf0191989
Publication Type	Research paper
PubMed ID	17329366
PubMed Abstract	Notch is a transmembrane receptor that mediates the cell-cell interactions necessary for many cell-fate decisions. Endocytic trafficking of Notch plays important roles in the activation and downregulation of this receptor. A Drosophila O-FucT-1 homolog, encoded by O-fut1, catalyzes the O-fucosylation of Notch, a modification essential for Notch signaling and ligand binding. It was recently proposed that O-fut1 acts as a chaperon for Notch in the endoplasmic reticulum and is required for Notch to exit the endoplasmic reticulum. Here, we report that O-fut1 has additional functions in the endocytic transportation of Notch. O-fut1 was indispensable for the constitutive transportation of Notch from the plasma membrane to the early endosome, which we show was independent of the O-fucosyltransferase activity of O-fut1. We also found that O-fut1 promoted the turnover of Notch, which consequently downregulated Notch signaling. O-fut1 formed a stable complex with the extracellular domain of Notch. In addition, O-fut1 protein added to conditioned medium and endocytosed was sufficient to rescue normal Notch transportation to the early endosome in O-fut1 knockdown cells. Thus, an extracellular interaction between Notch and O-fut1 is essential for the normal endocytic transportation of Notch. We propose that O-fut1 is the first example, except for ligands, of a molecule that is required extracellularly for receptor transportation by endocytosis.
DOI	10.1242/dev.02811
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Development
Title	Development
Publication Year	1987-
ISBN/ISSN	0950-1991
Data from Reference
Alleles (19)
	Avic\GFP^{ECFP.ER.Scer\UAS.T:Uuuu\KDEL} Avic\GFP^Pdi-74-1 Gmd^GS13045 Gmd^H43 Gmd^H78 N^{3.hs.T:Scer\GAL4,T:Hsim\VP16} N^55e11 N^{EGF.3.hs.T:Scer\GAL4,T:Hsim\VP16} N^MGIIa.MtnA N^ΔECN.MtnA O-fut1^4R6 O-fut1^{dsRNA.MtnA.cSa} O-fut1^G3.Scer\UAS O-fut1^{MtnA.T:Hsap\MYC} O-fut1^Scer\UAS.cSa O-fut1^{ΔER.Scer\UAS} Scer\GAL4^da.G32 Scer\GAL4^en-e16E Scer\GAL4^sd-SG29.1
Constructs (7)
	P{GAL4-da.G32} P{N⁺-GV.3} P{N^EGF-GV.3} P{UAS-ECFP-ER} P{UAS-O-fut1.G3} P{UAS-O-fut1.S} P{UAS-O-fut1.ΔER}
Genes (9)
	Avic\GFP en Gmd Hrs N O-fut1 Scer\GAL4 shg wg
Insertions (4)
	P{en2.4-GAL4}e16E P{GawB}sd^SG29.1 P{GSV6}Gmd^GS13045 P{PTT-un1}Pdi^74-1
Natural transposons (1)
	P-element