Naoyuki Taniguchi

RIKEN, Вако, Saitama, Japan

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Publications (815)3052.68 Total impact

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    Glycobiology 12/2015; 25(12):1323-1324. DOI:10.1093/glycob/cwv091 · 3.15 Impact Factor
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    ABSTRACT: The Human Disease Glycomics/Proteome Initiative (HGPI) is an activity in the Human Proteome Organization (HUPO) supported by leading researchers from international institutes and aims at development of disease-related glycomics/glycoproteomics analysis techniques. Since 2004, the initiative has conducted three pilot studies. The first two were N- and O-glycan analyses of purified transferrin and immunoglobulin-G and assessed the most appropriate analytical approach employed at the time. This paper describes the third study, which was conducted to compare different approaches for quantitation of N- and O-linked glycans attached to proteins in crude biological samples. The preliminary analysis on cell pellets resulted in wildly varied glycan profiles, which was probably the consequence of variations in the pre-processing sample preparation methodologies. However, the reproducibility of the data was not improved dramatically in the subsequent analysis on cell lysate fractions prepared in a specified method by one lab. The study demonstrated the difficulty of carrying out a complete analysis of the glycome in crude samples by any single technology and the importance of rigorous optimization of the course of analysis from preprocessing to data interpretation. It suggests that another collaborative study employing the latest technologies in this rapidly evolving field will help to realize the requirements of carrying out the large-scale analysis of glycoproteins in complex cell samples.
    Glycoconjugate Journal 10/2015; DOI:10.1007/s10719-015-9625-3 · 2.52 Impact Factor
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    ABSTRACT: β-Site amyloid precursor protein cleaving enzyme-1 (BACE1) is a protease essential for amyloid-β (Aβ) production in Alzheimer's disease (AD). BACE1 protein is known to be upregulated by oxidative stress-inducing stimuli but the mechanism for this upregulation remains to be clarified. We have recently found that BACE1 is modified with bisecting GlcNAc by N -acetylglucosaminyltransferase-III (GnT-III, encoded by Mgat3 gene) and that GnT-III deficiency reduces Aβ plaque formation in the brain by accelerating lysosomal degradation of BACE1. Therefore, we hypothesized that bisecting GlcNAc would stabilize BACE1 protein upon oxidative stress. In this study, we first show that Aβ deposition in the mouse brain induces oxidative stress concomitant with an increase in levels of BACE1 and bisecting GlcNAc. Furthermore, pro-oxidant treatment induces expression of BACE1 protein in wild-type mouse embryonic fibroblasts (MEFs), whereas it reduces BACE1 protein in GnT-III ( Mgat3 ) KO MEFs by accelerating lysosomal degradation of BACE1. We purified BACE1 from Neuro2A cells and performed LC-ESI-MS analysis for BACE1-derived glycopeptides and mapped bisecting GlcNAc-modified sites on BACE1. Point mutations at two N -glycosylation sites (N153 and N223) abolish the bisecting GlcNAc modification on BACE1. These mutations almost cancelled the enhanced BACE1 degradation seen in Mgat3(-/-) MEFs, indicating that bisecting GlcNAc on BACE1 indeed regulates its degradation. Finally, we show that traumatic brain injury-induced BACE1 upregulation is significantly suppressed in Mgat3(-/-) brain. These results highlight the role of bisecting GlcNAc in oxidative stress-induced BACE1 expression and offer a novel glycan-targeted strategy for suppressing Aβ generation.
    Biochemical Journal 10/2015; DOI:10.1042/BJ20150607 · 4.40 Impact Factor
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    ABSTRACT: In order to verify the protein enriched from pooled human sera to be a lung-specific protein surfactant protein-D (SP-D), we performed peptide mass fingerprinting (PMF)-based protein identification. MASCOT search results of the obtained PMF unequivocally demonstrated that it is identical to human SP-D. Meanwhile, we performed MALDI-QIT-TOF mass spectrometry-based N-glycomic analysis of the recombinant human SP-D produced in murine myeloma cells. The obtained mass spectra of N-glycans from the recombinant SP-D demonstrated that the recombinant protein is almost exclusively modified with core-fucosylated N-glycans. [1].
    09/2015; DOI:10.1016/j.dib.2015.09.017
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    ABSTRACT: Biological significance: It has been proposed that serum SP-D concentrations are predictive of COPD pathogenesis, but distinguishing between COPD patients and healthy individuals to establish a clear cut-off value is difficult because smoking status highly affects circulating SP-D levels. Herein, we focused on N-glycosylation in SP-D and examined whether or not N-glycosylation patterns in SP-D are associated with the pathogenesis of COPD. We performed an N-glycomic analysis of human serum SP-D and the results show that a core-fucose is present in its N-glycan. We also found that the N-glycosylation in serum SP-D was indeed altered in COPD, that is, fucosylation levels including core-fucosylation are significantly increased in COPD patients compared with non-COPD smokers. The severity of emphysema was positively associated with fucosylation levels in serum SP-D in smokers. Our findings shed new light on the discovery and/or development of a useful biomarker based on glycosylation changes for diagnosing COPD.
    Journal of proteomics 07/2015; 127. DOI:10.1016/j.jprot.2015.07.011 · 3.89 Impact Factor
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    ABSTRACT: E-cadherin is a central molecule in the process of gastric carcinogenesis and its posttranslational modifications by N-glycosylation have been described to induce a deleterious effect on cell adhesion associated with tumor cell invasion. However, the role that site-specific glycosylation of E-cadherin has in its defective function in gastric cancer cells needs to be determined. Using transgenic mice models and human clinical samples, we demonstrated that N-acetylglucosaminyltransferase V (GnT-V)-mediated glycosylation causes an abnormal pattern of E-cadherin expression in the gastric mucosa. In vitro models further indicated that, among the four potential N-glycosylation sites of E-cadherin, Asn-554 is the key site that is selectively modified with β1,6 GlcNAc-branched N-glycans catalyzed by GnT-V. This aberrant glycan modification on this specific asparagine site of E-cadherin was demonstrated to affect its critical functions in gastric cancer cells by affecting E-cadherin cellular localization, cis-dimer formation, molecular assembly and stability of the adherens junctions and cell-cell aggregation, which was further observed in human gastric carcinomas. Interestingly, manipulating this site-specific glycosylation, by preventing Asn-554 from receiving the deleterious branched structures, either by a mutation or by silencing GnT-V, resulted in a protective effect on E-cadherin, precluding its functional dysregulation and contributing to tumor suppression.Oncogene advance online publication, 20 July 2015; doi:10.1038/onc.2015.225.
    Oncogene 07/2015; DOI:10.1038/onc.2015.225 · 8.46 Impact Factor
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    ABSTRACT: Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade many extracellular matrix components and that have been implicated in the pathogenesis of various human diseases including cancer metastasis. Here, we screened MMP-9 inhibitors using photo-cross-linked chemical arrays, which can detect small-molecule ligand-protein interactions on a chip in a high-throughput manner. The array slides were probed sequentially with His-MMP-9, anti-His antibody, and a Cy5-labeled secondary antibody and then scanned with a microarray scanner. We obtained 27 hits among 24,275 compounds from the NPDepo library; 2 of the identified compounds (isoxazole compound 1 and naphthofluorescein) inhibited MMP-9 enzyme activity in vitro. We further explored 17 analogs of 1 and found that compound 18 had the strongest inhibitory activity. Compound 18 also inhibited other MMPs, including MMP-2, MMP-12, and MMP-13 and significantly inhibited cell migration in human fibrosarcoma HT1080 cells. These results suggest that 18 is a broad-spectrum MMP inhibitor.
    Bioscience Biotechnology and Biochemistry 05/2015; 79(10):1-6. DOI:10.1080/09168451.2015.1045829 · 1.06 Impact Factor
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    ABSTRACT: Core fucosylation is catalyzed by α1,6-fucosyltransferase (Fut8), which transfers a fucose residue to the innermost GlcNAc residue via α1,6-linkage on N-glycans in mammals. We previously reported that Fut8 knockout (Fut8-/-) mice showed a schizophrenia-like phenotype and a decrease in working memory. To understand the underlying molecular mechanism, we analyzed early-form long-term potentiation (E-LTP), which is closely related to learning and memory in the hippocampus. The scale of E-LTP induced by high frequency stimulation was significantly decreased in Fut8-/- mice. Tetraethylammonium-induced LTP showed no significant differences, suggesting that the decline in E-LTP was caused by post-synaptic events. Unexpectedly, the phosphorylation levels of calcium/calmodulin-dependent protein kinase II (CaMKII), an important mediator of learning and memory in post-synapses, were greatly increased in Fut8-/- mice. The expression levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) in the postsynaptic density were enhanced in Fut8-/- mice, although there were no significant differences in the total expression levels, implicating that AMPARs without core fucosylation might exist in an active state. The activation of AMPARs was further confirmed by Fura-2 calcium imaging using primary cultured neurons. Taken together, loss of core fucosylation on AMPARs enhanced their heteromerization, which might increase sensitivity for postsynaptic depolarization, and persistently activate N-methyl-D-aspartate receptors as well as Ca2+ influx and CaMKII, and then impair LTP. Copyright © 2015, The American Society for Biochemistry and Molecular Biology.
    Journal of Biological Chemistry 05/2015; 290(28). DOI:10.1074/jbc.M114.579938 · 4.57 Impact Factor
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    ABSTRACT: While many examples have been reported that glycoclusters interact with target lectins more strongly than single molecules of glycans, through multivalency effects, literature examples to support lectin interactions/modulations on cell surface and in live animals is quite rare. Our N-glycoclusters, which were efficiently prepared by immobilizing 16 molecules of the asparagine-linked glycans (N-glycans) onto a lysine-based dendron template through histidine-mediated Huisgen cycloaddition, were shown to efficiently detect platelet endothelial cell adhesion molecule (PECAM) on human umbilical vein endothelial cells (HUVEC) as a α(2-6)-sialylated oligosaccharides recognizing lectin. Furthermore, the identity of the N-glycans on our N-glycoclusters allowed control over organ-selective accumulation and serum clearance properties when intravenously injected into mice.
    Glycoconjugate Journal 05/2015; 32(7). DOI:10.1007/s10719-015-9594-6 · 2.52 Impact Factor
  • Yasuhiko Kizuka · Shinobu Kitazume · Keiko Sato · Naoyuki Taniguchi ·
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    ABSTRACT: β-Site amyloid precursor protein cleaving enzyme-1 (BACE1) is a central molecule in Alzheimer's disease (AD). It cleaves amyloid precursor protein (APP) to produce the toxic amyloid-β (Aβ) peptides. Thus, a novel BACE1 modulator could offer a new therapeutic strategy for AD. We report that C-type lectin-like domain family 4, member g (Clec4g, also designated as LSECtin) interacts with BACE1 in mouse brain and cultured cells. Overexpression of Clec4g suppressed BACE1-mediated Aβ generation, and affected the intracellular distribution of BACE1 but not its catalytic activity. These results highlight a novel role of Clec4g in negatively regulating BACE1 function. Copyright © 2015. Published by Elsevier B.V.
    FEBS letters 05/2015; 589(13). DOI:10.1016/j.febslet.2015.04.060 · 3.17 Impact Factor
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    ABSTRACT: ZG16p is a soluble mammalian lectin that interacts with mannose and heparan sulfate. Here we describe detailed analyses of the interactions of human ZG16p with mycobacterial phosphatidylinositol mannosides (PIMs), using glycan microarray and NMR. Pathogen-related glycan microarray analysis identified phosphatidylinositol mono- and di-mannosides (PIM1 and PIM2) as novel ligand candidates of ZG16p. Saturation Transfer Difference (STD) NMR and transferred NOE experiments with chemically synthesized PIM glycans indicate that PIMs preferentially interacts with ZG16p using the mannose residues. Binding site of PIMs is identified by chemical shift perturbation experiments using uniformly 15N-labeled ZG16p. NMR results with docking simulations suggest a binding mode of ZG16p and PIM glycan, which would help to consider the physiological role of ZG16p. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    ChemBioChem 04/2015; 16(10). DOI:10.1002/cbic.201500103 · 3.09 Impact Factor
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    ABSTRACT: O-GlcNAcylation is a reversible post-translational modification. O-GlcNAc addition and removal is catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. More recent evidence indicates that regulation of O-GlcNAcylation is important for inflammatory diseases and tumorigenesis. In this study, we revealed that O-GlcNAcylation was increased in the colonic tissues of dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced colitis-associated cancer (CAC) animal models. Moreover, the O-GlcNAcylation level was elevated in human CAC tissues compared with matched normal counterparts. To investigate the functional role of O-GlcNAcylation in colitis, we used OGA heterozygote mice, which have an increased level of O-GlcNAcylation. OGA+/- mice have higher susceptibility to DSS-induced colitis than OGA+/+ mice. OGA +/- mice exhibited a higher incidence of colon tumors than OGA+/+ mice. In molecular studies, elevated O-GlcNAc levels were shown to enhance the activation of NF-κB signaling through increasing the binding of RelA/p65 to its target promoters. We also found that Thr-322 and Thr352 in the p65-O-GlcNAcylation sites are critical for p65 promoter binding. These results suggest that the elevated O-GlcNAcylation level in colonic tissues contributes to the development of colitis and CAC by disrupting regulation of NF-κB-dependent transcriptional activity.
    Oncotarget 03/2015; 6(14). DOI:10.18632/oncotarget.3725 · 6.36 Impact Factor
  • Naoyuki Taniguchi · Yasuhiko Kizuka ·
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    ABSTRACT: Glycosylation is catalyzed by various glycosyltransferase enzymes which are mostly located in the Golgi apparatus in cells. These enzymes glycosylate various complex carbohydrates such as glycoproteins, glycolipids, and proteoglycans. The enzyme activity of glycosyltransferases and their gene expression are altered in various pathophysiological situations including cancer. Furthermore, the activity of glycosyltransferases is controlled by various factors such as the levels of nucleotide sugars, acceptor substrates, nucleotide sugar transporters, chaperons, and endogenous lectin in cancer cells. The glycosylation results in various functional changes of glycoproteins including cell surface receptors and adhesion molecules such as E-cadherin and integrins. These changes confer the unique characteristic phenotypes associated with cancer cells. Therefore, glycans play key roles in cancer progression and treatment. This review focuses on glycan structures, their biosynthetic glycosyltransferases, and their genes in relation to their biological significance and involvement in cancer, especially cancer biomarkers, epithelial-mesenchymal transition, cancer progression and metastasis, and therapeutics. Major N-glycan branching structures which are directly related to cancer are β1,6-GlcNAc branching, bisecting GlcNAc, and core fucose. These structures are enzymatic products of glycosyltransferases, GnT-V, GnT-III, and Fut8, respectively. The genes encoding these enzymes are designated as MGAT5 (Mgat5), MGAT3 (Mgat3), and FUT8 (Fut8) in humans (mice in parenthesis), respectively. GnT-V is highly associated with cancer metastasis, whereas GnT-III is associated with cancer suppression. Fut8 is involved in expression of cancer biomarker as well as in the treatment of cancer. In addition to these enzymes, GnT-IV and GnT-IX (GnT-Vb) will be also discussed in relation to cancer. © 2015 Elsevier Inc. All rights reserved.
    Advances in Cancer Research 03/2015; 126:11-51. DOI:10.1016/bs.acr.2014.11.001 · 5.32 Impact Factor
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    ABSTRACT: Ag recognition and Ab production in B cells are major components of the humoral immune response. In the current study, we found that the core fucosylation catalyzed by α1,6-fucosyltransferase (Fut8) was required for the Ag recognition of BCR and the subsequent signal transduction. Moreover, compared with the 3-83 B cells, the coalescing of lipid rafts and Ag-BCR endocytosis were substantially reduced in Fut8-knockdown (3-83-KD) cells with p31 stimulation and then completely restored by reintroduction of the Fut8 gene to the 3-83-KD cells. Indeed, Fut8-null (Fut8(-/-)) mice evoked a low immune response following OVA immunization. Also, the frequency of IgG-producing cells was significantly reduced in the Fut8(-/-) spleen following OVA immunization. Our results clearly suggest an unexpected mode of BCR function, in which the core fucosylation of IgG-BCR mediates Ag recognition and, concomitantly, cell signal transduction via BCR and Ab production. Copyright © 2015 by The American Association of Immunologists, Inc.
    The Journal of Immunology 02/2015; 194(6). DOI:10.4049/jimmunol.1402678 · 4.92 Impact Factor
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    ABSTRACT: Core fucosylation is an important post-translational modification, which is catalyzed by α1,6-fucosyltransferase (Fut8). Increased expression of Fut8 has been shown in diverse carcinomas including hepatocarcinoma. In this study, we investigated the role of Fut8 expression in liver regeneration by using the 70% partial hepatectomy (PH) model, and found that Fut8 is also critical for the regeneration of liver. Interestingly, we show that the Fut8 activities were significantly increased in the beginning of PH (~4d), but returned to the basal level in the late stage of PH. Lacking Fut8 led to delayed liver recovery in mice. This retardation mainly resulted from suppressed hepatocyte proliferation, as supported not only by a decreased phosphorylation level of epidermal growth factor (EGF) receptor and hepatocyte growth factor (HGF) receptor in the liver of Fut8(-/-) mice in vivo, but by the reduced response to exogenous EGF and HGF of the primary hepatocytes isolated from the Fut8(-/-) mice. Furthermore, an administration of L-fucose, which can increase GDP-fucose synthesis through a salvage pathway, significantly rescued the delayed liver regeneration of Fut8(+/-) mice. Overall, our study provides the first direct evidence for the involvement of Fut8 in liver regeneration.
    Scientific Reports 02/2015; 5:8264. DOI:10.1038/srep08264 · 5.58 Impact Factor
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    ABSTRACT: The β-site amyloid precursor protein cleaving enzyme-1 (BACE1), an essential protease for the generation of amyloid-β (Aβ) peptide, is a major drug target for Alzheimer's disease (AD). However, there is a concern that inhibiting BACE1 could also affect several physiological functions. Here, we show that BACE1 is modified with bisecting N-acetylglucosamine (GlcNAc), a sugar modification highly expressed in brain, and demonstrate that AD patients have higher levels of bisecting GlcNAc on BACE1. Analysis of knockout mice lacking the biosynthetic enzyme for bisecting GlcNAc, GnT-III (Mgat3), revealed that cleavage of Aβ-precursor protein (APP) by BACE1 is reduced in these mice, resulting in a decrease in Aβ plaques and improved cognitive function. The lack of this modification directs BACE1 to late endosomes/lysosomes where it is less colocalized with APP, leading to accelerated lysosomal degradation. Notably, other BACE1 substrates, CHL1 and contactin-2, are normally cleaved in GnT-III-deficient mice, suggesting that the effect of bisecting GlcNAc on BACE1 is selective to APP. Considering that GnT-III-deficient mice remain healthy, GnT-III may be a novel and promising drug target for AD therapeutics. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.
    EMBO Molecular Medicine 02/2015; 7(2). DOI:10.15252/emmm.201404438 · 8.67 Impact Factor
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    ABSTRACT: Unlabelled: Objecitive: Fucosyltransferase 8 (FUT8), the only enzyme responsible for the core α1,6-fucosylation of asparagine-linked oligosaccharides of glycoproteins, is a vital enzyme in cancer development and progression. We examined FUT8 expression in non-small cell lung cancers (NSCLCs) to analyze its clinical significance. We also examined the expression of guanosine diphosphate-mannose-4,6-dehydratase (GMD), which is imperative for the synthesis of fucosylated oligosaccharides. Methods: Using immunohistochemistry, we evaluated the expression of FUT8 and GMD in relation to patient survival and prognosis in potentially curatively resected NSCLCs. Results: High expression of FUT8 was found in 67 of 129 NSCLCs (51.9%) and was significantly found in non-squamous cell carcinomas (p = 0.008). High expression of FUT8 was associated with poor survival (p = 0.03) and was also a significant and independent unfavorable prognostic factor in patients with potentially curatively resected NSCLCs (p = 0.047). High expression of GMD was significantly associated with high FUT8 expression (p = 0.04). Conclusions: High expression of FUT8 is associated with an unfavorable clinical outcome in patients with potentially curatively resected NSCLCs, suggesting that FUT8 can be a prognostic factor. The analysis of FUT8 expression and its core fucosylated products may provide new insights for the therapeutic targets of NSCLCs.
    Oncology 01/2015; 88(5). DOI:10.1159/000369495 · 2.42 Impact Factor
  • Kazuki Nakajima · Naoyuki Taniguchi ·
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    ABSTRACT: Cellular glycosylation plays an important role in many biological processes, as well as in disease states such as diabetes and cancer. Nucleotide sugar s are donor substrates of glycosyltransferases and their availability and localization regulate glycosylation status. The nucleotide sugar level is controlled by cellular metabolic states. To investigate the fate of nucleotide sugars in glycosylation, two methods for monitoring nucleotide sugar metabolism, namely, ion-pair reversed-phase HPLC and LC-MS, have been previously described (Nakajima et al., Glycobiology 20(7):865–871, 2010; Mol Cell Proteomics (9):2468–2480, 2013). Using the HPLC method, cellular levels of eight unique nucleotide sugars were simultaneously determined. Using the LC-MS method, which is based on mass isotopomer analysis of nucleotide sugars metabolically labeled with 13C6-glucose, the metabolic pathways governing UDP-GlcNAc synthesis and utilization were characterized. Here, these strategies are reviewed and the biochemical significance of nucleotide sugars in cellular glycosylation is discussed.
    Glycoscience: Biology and Medicine, 01/2015: pages 103-110; , ISBN: 978-4-431-54840-9
  • Chi-Huey Wong · Naoyuki Taniguchi ·
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    ABSTRACT: This overview summarizes the current status and future perspectives in the field of glycoscience, with the focus on the integration of current knowledge obtained from genome and proteome research and the impact of such findings on human health and disease. The pathophysiological significance of glycan changes has been reported, and most of these findings can be found in the many chapters in this book. The roles of glycans in infectious diseases, differentiation and development, immune responses, cancer progression, neural communication, and many other intercellular recognition processes are the major topics in this book. Biomarker discovery and its validation of various diseases including cancer are a new challenge in this field. Therapeutics such as vaccines using glycan mimics, recombinant glycoproteins, or the modification of glycans are also new perspective for various diseases. In order to address these challenges, the chemo-enzymatic synthesis of glycans and more sensitive methods for glycan analysis by using NMR, mass spectrometry, imaging techniques, and bioinformatics are needed for the advancement of glycoscience. Finally, major future challenges of glycoscience are also listed in this overview.
    Glycoscience: Biology and Medicine, 01/2015: pages 11-14; , ISBN: 978-4-431-54840-9
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    ABSTRACT: Nutrient transporters are critical gate-keepers of extracellular metabolite entry into the cell. As integral membrane proteins, most transporters are N-glycosylated, and the N-glycans are remodeled in the Golgi apparatus. The Golgi branching enzymes N-acetylglucosaminyltransferases I, II, IV, V and avian VI (encoded by Mgat1, Mgat2, Mgat4a/b/c Mgat5 and Mgat6), each catalyze the addition of N-acetylglucosamine (GlcNAc) in N-glycans. Here, we asked whether N-glycan branching promotes nutrient transport and metabolism in immortal human HeLa carcinoma and non-malignant HEK293 embryonic kidney cells. Mgat6 is absent in mammals, but ectopic expression can be expected to add an additional β1,4-linked branch to N-glycans, and may provide evidence for functional redundancy of the N-glycan branches. Tetracycline (tet)-induced overexpression of Mgat1, Mgat5 and Mgat6 resulted in increased enzyme activity and increased N-glycan branching concordant with the known specificities of these enzymes. Tet-induced Mgat1, Mgat5 and Mgat6 combined with stimulation of hexosamine biosynthesis pathway (HBP) to UDP-GlcNAc, increased cellular metabolite levels, lactate and oxidative metabolism in an additive manner. We then tested the hypothesis that N-glycan branching alone might promote nutrient uptake when glucose (Glc) and glutamine are limiting. In low glutamine and Glc medium, tet-induced Mgat5 alone increased amino acids uptake, intracellular levels of glycolytic and TCA intermediates, as well as HEK293 cell growth. More specifically, tet-induced Mgat5 and HBP elevated the import rate of glutamine, although transport of other metabolites may be regulated in parallel. Our results suggest that N-glycan branching cooperates with HBP to regulate metabolite import in a cell autonomous manner, and can enhance cell growth in low-nutrient environments. © 2014 The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected] /* */
    Glycobiology 10/2014; 25(2). DOI:10.1093/glycob/cwu105 · 3.15 Impact Factor

Publication Stats

23k Citations
3,052.68 Total Impact Points


  • 2008-2015
    • RIKEN
      • • Global Research Cluster
      • • RIKEN-Max Planck Joint Research Center for Systems Chemical Biology
      • • Chemical Biology Team
      Вако, Saitama, Japan
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States
    • Seikagaku Corporation
      Edo, Tōkyō, Japan
    • Macquarie University
      • Department of Chemistry and Biomolecular Sciences
      Sydney, New South Wales, Australia
  • 2013
    • Waseda University
      • Faculty of Human Sciences
      Edo, Tōkyō, Japan
  • 1970-2013
    • Osaka University
      • • Institute of Scientific and Industrial Research
      • • Department of Disease Glycomics
      • • Division of Biochemistry
      • • Department of Internal Medicine
      Suika, Ōsaka, Japan
  • 1995-2011
    • Osaka City University
      • • Department of Biochemistry
      • • Graduate School of Medicine
      • • Second Department of Internal Medicine
      Ōsaka, Ōsaka, Japan
    • Osaka Medical Center and Research Institute for Maternal and Child Health
      Izumi, Ōsaka, Japan
    • University of Tsukuba
      Tsukuba, Ibaraki, Japan
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2005
    • Saga University
      • Department of Biomolecular Sciences
      Сага Япония, Saga, Japan
  • 2003
    • St. Jude Children's Research Hospital
      • Department of Developmental Neurobiology
      Memphis, Tennessee, United States
    • Yamagata University
      Ямагата, Yamagata, Japan
  • 2002
    • Nagoya University
      • Division of Neurology
      Nagoya, Aichi, Japan
    • Georgetown University
      • Department of Oncology
      Washington, Washington, D.C., United States
    • Hyogo College of Medicine
      • Department of Internal Medicine
      Nishinomiya, Hyōgo, Japan
    • Yale-New Haven Hospital
      • Department of Pathology
      New Haven, Connecticut, United States
  • 1999
    • Nagasaki University
      Nagasaki, Nagasaki, Japan
    • Kyorin University
      Edo, Tōkyō, Japan
    • Fukui University
      Hukui, Fukui, Japan
    • Osaka Police Hospital
      Ōsaka, Ōsaka, Japan
  • 1998
    • University of Helsinki
      Helsinki, Uusimaa, Finland
    • Osaka Rosai Hospital
      Ōsaka, Ōsaka, Japan
  • 1997
    • The Jikei University School of Medicine
      • Department of Biochemistry
      Edo, Tokyo, Japan
  • 1996
    • Aichi Cancer Center
      Ōsaka, Ōsaka, Japan
  • 1974-1995
    • Hokkaido University Hospital
      • • Division of Pediatrics
      • • Division of Neurosurgery
      • • Division of Internal Medicine II
      Sapporo-shi, Hokkaido, Japan
  • 1994
    • Niigata University
      Niahi-niigata, Niigata, Japan
    • Nara Medical University
      • Department of General Medicine
      Kashihara, Nara, Japan
  • 1991-1993
    • National Defense Medical College
      • Division of Hygiene
      Tokorozawa, Saitama, Japan
    • The University of Tokyo
      白山, Tōkyō, Japan
  • 1992
    • Sapporo Medical University
      • Department of Anatomy II
      Sapporo, Hokkaido, Japan
  • 1975-1990
    • Hokkaido University
      • • Department of Medicine II
      • • Cancer Institute
      • • Laboratory of Biochemistry
      • • Graduate School of Environmental Science
      • • Department of Pediatrics
      Sapporo, Hokkaidō, Japan
  • 1982
    • Asahikawa Medical University
      Асахикава, Hokkaido, Japan
  • 1977
    • Hokkaido University of Education
      Sapporo, Hokkaidō, Japan