Reference Report

Reference
Citation	Ishikawa, H.O., Higashi, S., Ayukawa, T., Sasamura, T., Kitagawa, M., Harigaya, K., Aoki, K., Ishida, N., Sanai, Y., Matsuno, K. (2005). Notch deficiency implicated in the pathogenesis of congenital disorder of glycosylation IIc. Proc. Natl. Acad. Sci. U.S.A. 102(51): 18532--18537. (Export to RIS)
FlyBase ID	FBrf0191442
Publication Type	Research paper
PubMed ID	16344471
PubMed Abstract	Congenital disorder of glycosylation IIc (CDG IIc), also termed leukocyte adhesion deficiency II, is a recessive syndrome characterized by slowed growth, mental retardation, and severe immunodeficiency. Recently, the gene responsible for CDG IIc was found to encode a GDP-fucose transporter. Here, we investigated the possible cause of the developmental defects in CDG IIc patients by using a Drosophila model. Biochemically, we demonstrated that a Drosophila homolog of the GDP-fucose transporter, the Golgi GDP-fucose transporter (Gfr), specifically transports GDP-fucose in vitro. To understand the function of the Gfr gene, we generated null mutants of Gfr in Drosophila. The phenotypes of the Drosophila Gfr mutants were rescued by the human GDP-fucose transporter transgene. Our phenotype analyses revealed that Notch (N) signaling was deficient in these Gfr mutants. GDP-fucose is known to be essential for the fucosylation of N-linked glycans and for O-fucosylation, and both fucose modifications are present on N. Our results suggest that Gfr is involved in the fucosylation of N-linked glycans on N and its O-fucosylation, as well as those of bulk proteins. However, despite the essential role of N O-fucosylation during development, the Gfr homozygote was viable. Thus, our results also indicate that the Drosophila genome encodes at least another GDP-fucose transporter that is involved in the O-fucosylation of N. Finally, we found that mammalian Gfr is required for N signaling in mammalian cultured cells. Therefore, our results implicate reduced N signaling in the pathology of CDG IIc.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Proc. Natl. Acad. Sci. U.S.A.
Title	Proceedings of the National Academy of Sciences of the United States of America
Publication Year	1915-
ISBN/ISSN	0027-8424
Data from Reference
Aberrations (1)
	Df(3R)Exel6147
Alleles (15)
	Avic\GFP^{ECFP.ER.Scer\UAS.T:Uuuu\KDEL} fng^Scer\UAS.cKa Gmd^H78 Hsap\SLC35C1^{R147C.Scer\UAS} Hsap\SLC35C1^Scer\UAS.cIa Hsap\SLC35C1^{Scer\UAS.T:Ivir\HA1} nac^EY01553 nac^Gfr-1 nac^Gfr-2 nac^{R125C.Scer\UAS} nac^Scer\UAS.cIa nac^{Scer\UAS.T:Ivir\HA1} Scer\GAL4^Act5C.PI Scer\GAL4^hs.PB Scer\GAL4^ptc-559.1
Constructs (10)
	P{Act5C-GAL4} P{GAL4-Hsp70.PB} P{UAS-ECFP-ER} P{UAS-fng.K} P{UAS-Gfr.I} P{UAS-Gfr.R125C} P{UAS-Gfr-HA.I} P{UAS-HsGfr.I} P{UAS-HsGfr.R147C} P{UAS-HsGfr-HA.I}
Genes (9)
	Avic\GFP fng Gmd Hsap\SLC35C1 N nac Scer\GAL4 T:Ivir\HA1 wg
Insertions (2)
	P{EPgy2}nac^EY01553 P{GawB}ptc^559.1
Natural transposons (1)
	P-element