title: Dual Roles of O-Glucose Glycans Redundant with Monosaccharide O-Fucose on Notch in Notch Trafficking.
abstract: Notch is a transmembrane receptor that mediates cell-cell interactions and controls various cell-fate specifications in metazoans. The extracellular domain of Notch contains multiple epidermal growth factor (EGF)-like repeats. At least five different glycans are found in distinct sites within these EGF-like repeats. The function of these individual glycans in Notch signaling has been investigated, primarily by disrupting their individual glycosyltransferases. However, we are just beginning to understand the potential functional interactions between these glycans. Monosaccharide O-fucose and O-glucose trisaccharide (O-glucose-xylose-xylose) are added to many of the Notch EGF-like repeats. In Drosophila, Shams adds a xylose specifically to the monosaccharide O-glucose. We found that loss of the terminal dixylose of O-glucose-linked saccharides had little effect on Notch signaling. However, our analyses of double mutants of shams and other genes required for glycan modifications revealed that both the monosaccharide O-glucose and the terminal dixylose of O-glucose-linked saccharides function redundantly with the monosaccharide O-fucose in Notch activation and trafficking. The terminal dixylose of O-glucose-linked saccharides and the monosaccharide O-glucose were required in distinct Notch trafficking processes: Notch transport from the apical plasma membrane to adherens junctions, and Notch export from the endoplasmic reticulum, respectively. Therefore, the monosaccharide O-glucose and terminal dixylose of O-glucose-linked saccharides have distinct activities in Notch trafficking, although a loss of these activities is compensated for by the presence of monosaccharide O-fucose. Given that various glycans attached to a protein motif may have redundant functions, our results suggest that these potential redundancies may lead to a serious underestimation of glycan functions.
authors.affiliation: From the Department of Biological Sciences, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043 and.
authors.forename: Kenjiroo
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: the Department of Biological Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-1500, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Ayukawa
authors.affiliation: the Department of Biological Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-1500, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ishio
authors.affiliation: From the Department of Biological Sciences, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043 and.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasamura
authors.affiliation: From the Department of Biological Sciences, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043 and.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamakawa
authors.affiliation: From the Department of Biological Sciences, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043 and kmatsuno@bio.sci.osaka-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuno
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D005643:Fucose / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D021381:Protein Transport / Q000502:physiology; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D014994:Xylose / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D005643:Fucose; D014994:Xylose; D005947:Glucose
keywords: Drosophila; Notch pathway; O-fucosetransferase; O-glucose; O-glycan; UDP-xylose synthase; cell signaling; fucosyltransferase; intracellular trafficking; xylosyltransferase