分子細胞化学・機能分子制御学

研究業績

最近の研究室の業績

2020年

  • Yesmin F, Bhuiyan RH, Ohmi Y, Ohkawa Y, Tajima O, Okajima T, Furukawa K, Furukawa K. Aminoglycosides are efficient reagents to induce readthrough of premature termination codon in mutant B4GALNT1 genes found in families of hereditary spastic paraplegia. J Biochem. in press
  • Alam SM, Tsukamoto Y, Ogawa M, Senoo Y, Ikeda K, Tashima Y, Hideyuki Takeuchi H and Okajima T. N-glycans on EGF domain-specific O-GlcNAc transferase (EOGT) facilitate EOGT maturation and peripheral endoplasmic reticulum localization. J Biol Chem. 295(25) 8560–8574
  • Urata Y, Saiki W,Tsukamoto Y, Sago H,Hibi H, Okajima T, Takeuchi H. Xylosyl Extension of O-Glucose Glycans on the Extracellular Domain of NOTCH1 and NOTCH2 Regulates Notch Cell Surface Trafficking. Cells (2020) 9(5), 1220; https://doi.org/10.3390/cells9051220
  • Ogawa M, Tashima Y, Sakaguchi Y, Takeuchi H, Okajima T. Contribution of extracellular O-GlcNAc to the stability of folded epidermal growth factor-like domains and Notch1 trafficking. Biochem Biophys Res Commun. 526:184-190. (2020)
  • Servián-Morilla E, Cabrera-Serrano M, Johnson K, Pandey A, Ito A, Rivas E, Chamova T, Muelas N, Mongini T, Nafissi S, Claeys KG, Grewal RP, Takeuchi M, Hao H, Bönnemann C, Lopes Abath Neto O, Medne L, Brandsema J, Töpf A, Taneva A, Vilchez JJ, Tournev I, Haltiwanger RS, Takeuchi H, Jafar-Nejad H, Straub V, and Paradas C. POGLUT1 biallelic mutations cause myopathy with reduced satellite cells, α-dystroglycan hypoglycosylation and a distinctive radiological pattern. Acta Neuropathol.  2020 Mar; 139 (3): 565-82.
  • Urata Y and Takeuchi H.  Effects of Notch glycosylation on health and diseases. Dev Growth Differ 2020 Jan; 62 (1): 35-48.

2019年

  • Ralser DJ, Takeuchi H, Fritz G, Basmanav FB, Effern M, Sivalingam S, El-Shabrawi-Caelen L, Degirmentepe EN, Kocatürk E, Singh M, Booken N, Spierings NMK, Schnabel V, Heineke A, Knuever J, Wolf S, Wehner M, Tronnier M, Leverkus M, Tantcheva-Poór I, Wenzel J, Oji V, Has C, Hölzel M, Frank J, Haltiwanger RS, and Betz RC.  Altered Notch signaling in Dowling-Degos disease: Additional mutations in POGLUT1 and further insights into disease pathogenesis. J Invest Dermatol  2019 139: 960-964.
  • Takeuchi H.  Notch-Modifying Protein O-Glucosyltransferase 1 (POGLUT1): Specificities, Structures, and Human Disease Implications. Trends in Glycoscience and Glycotechnology 2019; 31: E49-E52.
  • Hashimoto N, Ito S, Tsuchida A, Bhuiyan RH, Okajima T, Yamamoto A, Furukawa K, Ohmi Y, Furukawa K. The ceramide moiety of disialoganglioside (GD3) is essential for GD3 recognition by the sialic acid-binding lectin SIGLEC7 on the cell surface. J Biol Chem. 294(28):10833-10845. (2019)
  • Bhuiyan RH, Ohmi Y, Ohkawa Y, Zhang P, Takano M, Hashimoto N, Okajima T, Furukawa K, Furukawa K. Loss of Enzyme Activity in Mutated B4GALNT1 Gene Products in Patients with Hereditary Spastic Paraplegia Results in Relatively Mild Neurological Disorders: Similarity with Phenotypes of B4galnt1 Knockout Mice. Neuroscience. 397:94-106.  (2019)
  • Yu H and Takeuchi H. Protein O-glucosylation: another essential role of glucose in biology. Curr Opin Struct Biol 2019 Jan; 56: 64-71.

2018年

  • Takeuchi H*, Schneider M*, Williamson DB, Ito A, Takeuchi M, Handford PA, and Haltiwanger RS.  Two novel protein O-glucosyltransferases that modify sites distinct from POGLUT1 and affect Notch trafficking and signaling. Proc Natl Acad Sci USA 2018; 115 (36): E8395-402.
  • Ogawa M, Okajima T. Dissection and Whole Mount Staining of Retina from Neonatal Mice. Bio-101  DOI:   10.21769/BioProtoc.3034 (2018)
  • Zhang A, Sawaguchi S, Wan E, Ogawa M, Okajima T. Isolation of Murine Brain and Lung Microvascular Endothelial Cells   Bio-101  DOI:   10.21769/BioProtoc.2984 (2018)
  • Wan E, Ogawa M, Okajima T.  A Blood-retina Barrier Permeability Assay in Young Mice Using Sulfo-NHS-LC-biotin. Bio-101 (2018) DOI:   10.21769/BioProtoc.3064
  • Ogawa M, Senoo Y, Ikeda K, Takeuchi H, Okajima T. Structural Divergence in O-GlcNAc Glycans Displayed on Epidermal Growth Factor-like Repeats of Mammalian Notch1. Molecules.;23(7). pii: E1745. (2018)
  • Takeuchi H, Wong D, Schneider M, Freeze HH, Takeuchi M, Berardinelli SJ, Ito A, Lee H, Nelson SF, and Haltiwanger RS. Variant in human POFUT1 reduces enzymatic activity and likely causes a recessive microcephaly, global developmental delay with cardiac and vascular features. Glycobiology 2018 May; 28 (5): 276-83. (Recommended by Faculty of 1000 Prime)
  • Fujihira H, Usami K, Matsuno K, Takeuchi H, Denda-Nagai K, Furukawa JI, Shinohara Y, Takada A, Kawaoka Y, and Irimura T. A critical domain of Ebolavirus envelope glycoprotein determines glycoform and infectivity. Sci Rep 2018 Apr; 8 (1): 5495.
  • Schneider M, Kumar V, Nordstrom LU, Feng L, Takeuchi H, Hao H, Luca VC, Garcia KC, Stanley P, Wu P, and Haltiwanger RS. Inhibition of Delta-induced Notch signaling using fucose analogs. Nature Chem Biol 2018 Jan; 14 (1): 65-71.

2017年

  • Weh E, Takeuchi H, Muheisen S, Haltiwanger RS, and Semina EV. Functional characterization of zebrafish orthologs of the human Beta 3-Glucosyltransferase B3GLCT gen mutated in Peters Plus syndrome. Plos One 2017 Sep; 12 (9): e0184903.
  • Takeuchi H*, Yu H*, Hao H, Takeuchi M, Ito A, Li H, and Haltiwanger RS. O-Glycosylation modulates the stability of epidermal growth factor-like repeats and thereby regulates Notch trafficking. J Biol Chem  2017 Sep; 292 (38): 15964-73. (*: Equal contribution)
  • Sawaguchi S, Ogawa M, Okajima T.  Protocol for Notch-ligand Binding Assays Using Dynabeads. Bio-protocol 7: e2582 (2017)
  • Sawaguchi S, Varshney S, Ogawa M, Sakaidani Y, Yagi H, Takeshita K, Murohara T, Kato K, Sundaram S, Stanley P and Okajima T. O-GlcNAc on NOTCH1 EGF Repeats Regulates Ligand-Induced Notch Signaling and Vascular Development in Mammals. eLife 6: e24419. (2017)
  • Sheikh MO, Halmo SM, Patel S, Middleton D, Takeuchi H, Schafer CM, West CM, Haltiwanger RS, Avci FY, Moremen KW, and Wells L.  Rapid screening of sugar-nucleotide donor specificities of putative glycosyltransferases. Glycobiology 2017 Mar; 27 (3): 206-12.
  • Hubmacher D, Schneider M, Berardinelli SJ, Takeuchi H, Willard B, Reinhardt DP, Haltiwanger RS, and Apte SS. Unusual life cycle and impact on microfibril assembly of ADAMTS17, a secreted metalloprotease mutated in genetic eye disease. Sci Rep 2017 Feb; 7: 41871.

2016年

  • Servián-Morilla E*, Takeuchi H*, Lee TV*, Clarimon J, Mavillard F, Area-Gómez E, Rivas E, Nieto-González JL, Rivero MC, Cabrera-Serrano M, Gómez-Sánchez L, Martínez-López JA, Estrada B, Márquez C, Morgado Y, Suárez-Calvet X, Pita G, Bigot A, Gallardo E, Fernández-Chacón R, Hirano M, Haltiwanger RS, Jafar-Nejad H, Paradas C. A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss. EMBO Mol Med  2016 Nov; 8 (11): 1289-1309. (*: Equal contribution)
  • Yu H*, Takeuchi H*, Takeuchi M, Kantharia J, Haltiwanger RS#, and Li H#.  Structural analysis of Notch-regulating Rumi reveals basis for pathogenic mutations. Nature Chem Biol  2016 Sep; 12 (9): 735-40. (*: Equal contribution, #: Co-corresponding author)
  • Benz BA, Nandadasa S, Takeuchi M, Grady RC, Takeuchi H, LoPilato RK, Kakuda S, Somerville RPT, Apte SS, Haltiwanger RS#, and Holdener BC#.  Genetic and biochemical evidence that gastrulation defects in Pofut2 mutants result from defects in ADAMTS9 secretion. Dev Biol 2016 Aug; 416 (1): 111-22. (#: Co-corresponding author)
  • Kaneko K, Ohkawa Y, Hashimoto N, Ohmi Y, Kotani N, Honke K, Ogawa M, Okajima T, Furukawa K, Furukawa K. Neogenin defined as a GD3-associated molecule by enzyme-mediated activation of radical sources confers malignant properties via intra-cytoplasmic domain in melanoma cells. J Biol Chem. 291, 16630-16643 (2016)
  • Bhuiyan RH, Kondo Y, Yamaguchi T, Tokuda N, Ohkawa Y, Hashimoto N, Ohmi Y, Yamauchi Y, Furukawa K, Okajima T, Furukawa K. Expression analysis of 0-series gangliosides in human cancer cell lines with monoclonal antibodies generated using knockout mice of ganglioside synthase genes. Glycobiology. 26, 984-998. (2016)
  • Yamaguchi T, Yamauchi Y, Furukawa K, Ohmi Y, Ohkawa Y, Zhang Q, Okajima T, Furukawa K. Expression of B4GALNT1, an essential glycosyltransferase for the synthesis of complex gangliosides, suppresses BACE1 degradation and modulates APP processing.
    Sci Rep. 30:34505. (2016) 
  • Ji S, Tokizane K, Ohkawa Y, Ohmi Y, Banno R, Okajima T, Kiyama H, Furukawa K, Furukawa K. Increased a-series gangliosides positively regulate leptin/Ob receptor-mediated signals in hypothalamus of GD3 synthase-deficient mice. Biochem Biophys Res Commun. 479:453-460. (2016)
  • Nogimori K, Hori T, Kawaguchi K, Fukui T, Mii S, Nakada H, Matsumoto Y, Yamauchi Y, Takahashi M, Furukawa K, Okajima T, Yokoi K, Hasegawa Y, Furukawa K. Increased expression levels of ppGalNAc-T13 in lung cancers: Significance in the prognostic diagnosis. Int J Oncol. 49: 1369-1376. (2016) 
  • Valero-Gonzalez J*, Leonhard-Melief C*, Lira-Navarrete E, Jimenez-Oses G, Hernandez-Ruiz C, Pallares CP, Yruela I, Vasudevan D, Lostao A, Corzana F, Takeuchi H, Haltiwanger RS, and Hurtado-Gerrero R.  A proactive role of water molecules in acceptor recognition by Protein-O-fucosyltransferase 2. Nature Chem Biol 2016 Apr; 12 (4): 240-6. (*: Equal contribution) 

研究メンバーの過去の主要業績

  • Ogawa M, Sawaguchi S, Kawai T, Nadano D, Matsuda T, Yagi H, Kato K, Furukawa K, Okajima T. Impaired O-linked N-acetylglucosaminylation in the endoplasmic reticulum by mutated EGF domain-specific O-linked N-acetylglucosamine transferase found in Adams-Oliver syndrome. J Biol Chem 290:2137-2149 (2015)
  • Yu H, Takeuchi M, Kantharia J, LeBarron J, London E, Bakker H, Haltiwanger RS, Li H, and Takeuchi H.  Notch-modifying xylosyltransferase structures support an SNi-like retaining mechanism. Nature Chem Biol  2015 Nov; 11 (11): 847-54.
  • Sakaidani Y, Nomura T, Matsuura A, Ito M, Suzuki E, Murakami K, Nadano D, Matsuda T, Furukawa K, Okajima T. O-linked-N-acetylglucosamine on extracellular protein domains mediates epithelial cell-matrix interactions. Nat Commun 2:583 (2011)
  • Takeuchi H, Fernández-Valdivia RC, Caswell DS, Nita-Lazar A, Rana NA, Macnaughtan MA, Jafar-Nejad H, and Haltiwanger RS. Rumi functions as both a protein O-glucosyltransferase and a protein O-xylosyltransferase. Proc Natl Acad Sci USA  2011 Oct; 108 (40): 16600-5.
  • Ishikawa HO, Takeuchi H, Haltiwanger RS, and Irvine KD.  Four-jointed is a Golgi kinase that phosphorylates a subset of cadherin domains. Science 2008 Jul; 321 (5887): 401-4. (Recommended by Faculty of 1000)
  • Acar M*, Jafar-Nejad H*, Takeuchi H*, Rajan A, Ibrani D, Rana NA, Pan H, Haltiwanger RS, and Bellen H.  Rumi, a CAP10 domain protein, is a glycosyltransferase that modifies Notch and is required for Notch signaling. Cell 2008 Jan; 132 (2): 247-58. (*: Equal contribution, Recommended by Faculty of 1000)
  • Matsuura A, Ito M, Sakaidani Y, Kondo T, Murakami K, Furukawa K, Nadano D, Matsuda T, Okajima T. O-linked N-acetylglucosamine is present on the extracellular domain of notch receptors. J Biol Chem 283:35486-35495 (2008)
  • Okajima T, Reddy B, Matsuda T, Irvine KD. Contributions of chaperone and glycosyltransferase activities of O-fucosyltransferase 1 to Notch signaling. BMC Biol 6:1 (2008)
  • Okajima T, Xu A, Lei L, Irvine KD. Chaperone activity of protein O-fucosyltransferase 1 promotes notch receptor folding. Science 307:1599-1603 (2005)
  • Okajima T, Irvine KD. Regulation of notch signaling by O-linked fucose. Cell 111:893-904 (2002)