RRC ID |
36279
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著者 |
Ishio A, Sasamura T, Ayukawa T, Kuroda J, Ishikawa HO, Aoyama N, Matsumoto K, Gushiken T, Okajima T, Yamakawa T, Matsuno K.
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タイトル |
O-fucose monosaccharide of Drosophila Notch has a temperature-sensitive function and cooperates with O-glucose glycan in Notch transport and Notch signaling activation.
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ジャーナル |
J Biol Chem
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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.
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巻・号 |
290(1)
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ページ |
505-19
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公開日 |
2015-1-2
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DOI |
10.1074/jbc.M114.616847
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PII |
S0021-9258(20)57947-7
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PMID |
25378397
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PMC |
PMC4281752
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MeSH |
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
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IF |
4.238
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引用数 |
31
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WOS 分野
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BIOCHEMISTRY & MOLECULAR BIOLOGY
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リソース情報 |
ショウジョウバエ |
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