RRC ID 36279
著者 Ishio A, Sasamura T, Ayukawa T, Kuroda J, Ishikawa HO, Aoyama N, Matsumoto K, Gushiken T, Okajima T, Yamakawa T, Matsuno K.
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.
ジャーナル J Biol Chem
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.
巻・号 290(1)
ページ 505-19
公開日 2015-1-2
DOI 10.1074/jbc.M114.616847
PII S0021-9258(20)57947-7
PMID 25378397
PMC PMC4281752
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
IF 4.238
引用数 31
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
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