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PMID:19948734

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Citation

Ishikawa, HO, Ayukawa, T, Nakayama, M, Higashi, S, Kamiyama, S, Nishihara, S, Aoki, K, Ishida, N, Sanai, Y and Matsuno, K (2010) Two pathways for importing GDP-fucose into the endoplasmic reticulum lumen function redundantly in the O-fucosylation of Notch in Drosophila. J. Biol. Chem. 285:4122-9

Abstract

Notch is a transmembrane receptor that shares homology with proteins containing epidermal growth factor-like repeats and mediates the cell-cell interactions necessary for many cell fate decisions. In Drosophila, O-fucosyltransferase 1 catalyzes the O-fucosylation of these epidermal growth factor-like repeats. This O-fucose elongates, resulting in an O-linked tetrasaccharide that regulates the signaling activities of Notch. Fucosyltransferases utilize GDP-fucose, which is synthesized in the cytosol, but fucosylation occurs in the lumen of the endoplasmic reticulum (ER) and Golgi. Therefore, GDP-fucose uptake into the ER and Golgi is essential for fucosylation. However, although GDP-fucose biosynthesis is well understood, the mechanisms and intracellular routes of GDP-fucose transportation remain unclear. Our previous study on the Drosophila Golgi GDP-fucose transporter (Gfr), which specifically localizes to the Golgi, suggested that another GDP-fucose transporter(s) exists in Drosophila. Here, we identified Efr (ER GDP-fucose transporter), a GDP-fucose transporter that localizes specifically to the ER. Efr is a multifunctional nucleotide sugar transporter involved in the biosynthesis of heparan sulfate-glycosaminoglycan chains and the O-fucosylation of Notch. Comparison of the fucosylation defects in the N-glycans in Gfr and Efr mutants revealed that Gfr and Efr made distinct contributions to this modification; Gfr but not Efr was crucial for the fucosylation of N-glycans. We also found that Gfr and Efr function redundantly in the O-fucosylation of Notch, although they had different localizations and nucleotide sugar transportation specificities. These results indicate that two pathways for the nucleotide sugar supply, involving two nucleotide sugar transporters with distinct characteristics and distributions, contribute to the O-fucosylation of Notch.

Links

PubMed PMC2823552 Online version:10.1074/jbc.M109.016964

Keywords

Animals; Biological Transport; Blotting, Western; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/genetics; Drosophila melanogaster/metabolism; Endoplasmic Reticulum/metabolism; Glycosaminoglycans/biosynthesis; Glycosylation; Golgi Apparatus/metabolism; Guanosine Diphosphate Fucose/metabolism; Immunohistochemistry; Monosaccharide Transport Proteins/genetics; Monosaccharide Transport Proteins/metabolism; Mutation; Nucleotide Transport Proteins/genetics; Nucleotide Transport Proteins/metabolism; Polysaccharides/metabolism; Receptors, Notch/genetics; Receptors, Notch/metabolism; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:FUCT1

located_in

GO:0005794: Golgi apparatus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:FUCT1

involved_in

GO:0036071: N-glycan fucosylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:S35B4

NOT|enables

GO:0005456: CMP-N-acetylneuraminate transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:S35B4

enables

GO:0005457: GDP-fucose transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:S35B4

NOT|enables

GO:0005458: GDP-mannose transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:S35B4

NOT|enables

GO:0005460: UDP-glucose transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:S35B4

NOT|enables

GO:0005461: UDP-glucuronic acid transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:S35B4

enables

GO:0005462: UDP-N-acetylglucosamine transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:S35B4

enables

GO:0005464: UDP-xylose transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:S35B4

located_in

GO:0005783: endoplasmic reticulum

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:S35B4

located_in

GO:0016021: integral component of membrane

ECO:0000255: match to sequence model evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:S35B4

involved_in

GO:0015790: UDP-xylose transmembrane transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:S35B4

NOT|involved_in

GO:0015787: UDP-glucuronic acid transmembrane transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:S35B4

NOT|involved_in

GO:0015786: UDP-glucose transmembrane transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:S35B4

involved_in

GO:0015783: GDP-fucose transmembrane transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:S35B4

NOT|involved_in

GO:0015782: CMP-N-acetylneuraminate transmembrane transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:S35B4

involved_in

GO:0015012: heparan sulfate proteoglycan biosynthetic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:S35B4

involved_in

GO:0036084: GDP-fucose import into endoplasmic reticulum lumen

ECO:0000305: curator inference used in manual assertion

GO:0005457,GO:0005783

P

Seeded From UniProt

complete

DROME:S35B4

involved_in

GO:0036066: protein O-linked fucosylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:S35B4

NOT|involved_in

GO:1990570: GDP-mannose transmembrane transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:S35B4

involved_in

GO:1990569: UDP-N-acetylglucosamine transmembrane transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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