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PMID:25378397

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Citation

Ishio, A, Sasamura, T, Ayukawa, T, Kuroda, J, Ishikawa, HO, Aoyama, N, Matsumoto, K, Gushiken, T, Okajima, T, Yamakawa, T and Matsuno, K (2015) O-fucose monosaccharide of Drosophila Notch has a temperature-sensitive function and cooperates with O-glucose glycan in Notch transport and Notch signaling activation. J. Biol. Chem. 290:505-19

Abstract

Notch (N) is a transmembrane receptor that mediates the cell-cell interactions necessary for many cell fate decisions. N has many epidermal growth factor-like repeats that are O-fucosylated by the protein O-fucosyltransferase 1 (O-Fut1), and the O-fut1 gene is essential for N signaling. However, the role of the monosaccharide O-fucose on N is unclear, because O-Fut1 also appears to have O-fucosyltransferase activity-independent functions, including as an N-specific chaperon. Such an enzymatic activity-independent function could account for the essential role of O-fut1 in N signaling. To evaluate the role of the monosaccharide O-fucose modification in N signaling, here we generated a knock-in mutant of O-fut1 (O-fut1(R245A knock-in)), which expresses a mutant protein that lacks O-fucosyltransferase activity but maintains the N-specific chaperon activity. Using O-fut1(R245A knock-in) and other gene mutations that abolish the O-fucosylation of N, we found that the monosaccharide O-fucose modification of N has a temperature-sensitive function that is essential for N signaling. The O-fucose monosaccharide and O-glucose glycan modification, catalyzed by Rumi, function redundantly in the activation of N signaling. We also showed that the redundant function of these two modifications is responsible for the presence of N at the cell surface. Our findings elucidate how different forms of glycosylation on a protein can influence the protein's functions.

Links

PubMed PMC4281752 Online version:10.1074/jbc.M114.616847

Keywords

Animals; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/genetics; Drosophila melanogaster/metabolism; Fucose/chemistry; Fucose/metabolism; Fucosyltransferases/genetics; Fucosyltransferases/metabolism; Gene Knock-In Techniques; Glucose/chemistry; Glucose/metabolism; Glucosyltransferases/genetics; Glucosyltransferases/metabolism; Glycosylation; Polysaccharides/chemistry; Polysaccharides/metabolism; Protein Folding; Protein Processing, Post-Translational; Protein Transport; Receptors, Notch/genetics; Receptors, Notch/metabolism; Signal Transduction/genetics; Temperature

Significance

Annotations

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

DROME:OFUT1

involved_in

GO:0045747: positive regulation of Notch signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:RUMI

involved_in

GO:0045747: positive regulation of Notch signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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