title: O-linked-N-acetylglucosamine on extracellular protein domains mediates epithelial cell-matrix interactions.
abstract: The O-linked-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and nuclear proteins regulates basic cellular functions and is involved in the aetiology of diabetes and neurodegeneration. This intracellular O-GlcNAcylation is catalyzed by a single O-GlcNAc transferase, OGT. Here we report a novel OGT, EOGT, responsible for extracellular O-GlcNAcylation. Although both OGT and EOGT are regulated by hexosamine flux, EOGT localizes to the lumen of the endoplasmic reticulum and transfers GlcNAc to epidermal growth factor-like domains in an OGT-independent manner. Loss of Eogt gives phenotypes similar to those caused by defects in the apical extracellular matrix. Dumpy (Dp), a membrane-anchored extracellular protein, is O-GlcNAcylated, and EOGT is required for Dp-dependent epithelial cell-matrix interactions. Thus, O-GlcNAcylation of secreted and membrane glycoproteins is a novel mediator of cell-cell or cell-matrix interactions at the cell surface.
authors.affiliation: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Sakaidani
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nomura
authors.forename: Aiko
authors.initials: A
authors.lastname: Matsuura
authors.forename: Makiko
authors.initials: M
authors.lastname: Ito
authors.forename: Emiko
authors.initials: E
authors.lastname: Suzuki
authors.forename: Kosuke
authors.initials: K
authors.lastname: Murakami
authors.forename: Daita
authors.initials: D
authors.lastname: Nadano
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Matsuda
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Okajima
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000215:Acylation; D000595:Amino Acid Sequence; D000818:Animals; D002450:Cell Communication / Q000235:genetics*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D006595:Hexosamines / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D011485:Protein Binding; D011499:Protein Processing, Post-Translational / Q000235:genetics; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection
chemical_list: C411950:DPY protein, Drosophila; D029721:Drosophila Proteins; D016326:Extracellular Matrix Proteins; D006595:Hexosamines; D004815:Epidermal Growth Factor; C585194:Eogt protein, Drosophila; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D000117:Acetylglucosamine