A5060576443- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Muscle Physiology and Disorders
- Carbohydrate Chemistry and Synthesis
- Cell Adhesion Molecules Research
- Regulation of Appetite and Obesity
- Ubiquitin and proteasome pathways
- Invertebrate Immune Response Mechanisms
- Immune Response and Inflammation
- Lipid Membrane Structure and Behavior
- Caveolin-1 and cellular processes
- Biochemical Analysis and Sensing Techniques
- Sphingolipid Metabolism and Signaling
- Enzyme Production and Characterization
- Virus-based gene therapy research
- Signaling Pathways in Disease
- Protease and Inhibitor Mechanisms
- RNA regulation and disease
- Mosquito-borne diseases and control
- Lipid metabolism and disorders
- Antimicrobial Peptides and Activities
- Venomous Animal Envenomation and Studies
- Diabetes and associated disorders
- Hereditary Neurological Disorders
- Microbial Community Ecology and Physiology
Tohoku Medical and Pharmaceutical University
2014-2024
University of Iowa
2009-2016
Howard Hughes Medical Institute
2009-2016
Komatsu (Japan)
2014
RIKEN
2013
Osaka University
2003-2008
Kyushu University
2000-2004
Fukuoka University
1999
Meiji (Japan)
1992
Going LARGE Dystroglycan (DG) is a highly glycosylated extracellular matrix (ECM) receptor involved in variety of physiological processes, including maintenance skeletal muscle membrane integrity and the structure function central nervous system. The like-acetylglucosaminyltransferase (LARGE) responsible for posttranslational modifications alpha-dystroglycan (α-DG) required its function. Now, Inamori et al. (p. 93 ) demonstrate that bifunctional glycosyltransferase able to transfer xylose...
Dystroglycan is a cell membrane receptor that organizes the basement by binding ligands in extracellular matrix. Proper glycosylation of α-dystroglycan (α-DG) subunit essential for these activities, and lack thereof results neuromuscular disease. Currently, neither glycan synthesis pathway nor roles many known or putative glycosyltransferases are this process well understood. Here we show FKRP, FKTN, TMEM5 B4GAT1 (formerly as B3GNT1) localize to Golgi contribute O-mannosyl...
N-Acetylglucosaminyltransferase V (GnT-V) catalyzes the addition of β1,6-GlcNAc branching N-glycans, which contributes to metastasis. III (GnT-III) formation a bisecting GlcNAc structure in resulting suppression It has long been hypothesized that GnT-V product by action GnT-III would also exist vivo, will consequently lead inhibition biological functions GnT-V. To test this, we draw comparison among MKN45 cells, were transfected with GnT-III, GnT-V, or both, respectively. We found α3β1...
The interaction between epithelial cells and the extracellular matrix is crucial for tissue architecture function compromised during cancer progression. Dystroglycan a membrane receptor that mediates interactions basement membranes in various epithelia. In many epithelium-derived cancers, beta-dystroglycan expressed, but alpha-dystroglycan not detected. Here we report correctly expressed trafficked to cell lacks laminin binding as result of silencing like-acetylglucosaminyltransferase...
Bacterial lipopolysaccharide (LPS)-induced exocytosis of granular hemocytes is a key component the horseshoe crab's innate immunity to infectious microorganisms; stimulation by LPS induces secretion various defense molecules from hemocytes. Using previously uncharacterized assay for exocytosis, we clearly show that respond only and not other pathogen-associated molecular patterns, such as β-1,3-glucans peptidoglycans. Furthermore, protein called factor C, an LPS-recognizing serine protease...
In demyelinating diseases such as multiple sclerosis, a critical problem is failure of remyelination, which important for protecting axons against degeneration and restoring conduction deficits. However, the underlying mechanism demyelination/remyelination remains unclear. <i>N</i>-acetylglucosaminyltransferase-IX (GnT-IX; also known GnT-Vb) brain-specific glycosyltransferase that catalyzes branched formation <i>O</i>-mannosyl glycan structures. <i>O</i>-Mannosylation α-dystroglycan its...
LARGE-dependent modification enables α-dystroglycan (α-DG) to bind its extracellular matrix ligands. Mutations in the LARGE gene and several others involved O-mannosyl glycan synthesis have been identified congenital limb-girdle muscular dystrophies that are characterized by perturbed glycosylation reduced ligand-binding affinity of α-DG. is a bifunctional glycosyltransferase alternately transfers xylose glucuronic acid, thereby generating heteropolysaccharides on α-DG confer ligand binding....
Various computational methods have been developed to predict the pathogenicity of missense variants, which is crucial for diagnosing rare diseases. Recently, we introduced VarMeter, a diagnostic tool predicting variant based on normalized solvent-accessible surface area (nSASA) and mutation energy calculated from AlphaFold 3D models, validated it arylsulfatase L. To evaluate broader applicability VarMeter enhance its predictive accuracy, here analyzed 296 pathogenic 240 benign variants...
A novel β1,6-N-acetylglucosaminyltransferase (β1, 6GnT) cDNA was identified by a BLAST search using the amino acid sequence of human GnT-V as query. The full-length determined combination 5′-rapid amplification end analysis and further data base search. open reading frame encodes 792 protein with type II membrane structure typical glycosyltransferases. entire identity to is 42%. When pyridylaminated (PA) agalacto biantennary N-linked oligosaccharide used an acceptor substrate, recombinant...
Significance Dystroglycan (DG) is an extracellular matrix receptor that linked to the cytoskeleton and critical for development of skeletal muscle. DG deficiency throughout associated with multiple pathological features muscular dystrophy. However, direct consequence disruption in mature muscle not known. Here, we investigate muscles transgenic mice after genetic knockdown at maturity. The results demonstrate early susceptibility contraction-induced injury accompanied by reduced passive...
Article7 May 2020Open Access Homeostatic and pathogenic roles of GM3 ganglioside molecular species in TLR4 signaling obesity Hirotaka Kanoh Division Glycopathology, Institute Molecular Biomembrane Glycobiology, Tohoku Medical Pharmaceutical University, Sendai, Japan Search for more papers by this author Takahiro Nitta Shinji Go Kei-ichiro Inamori Lucas Veillon Wataru Nihei Mayu Fujii Department Chemistry, Graduate School Science, Osaka Osaka, Kazuya Kabayama Atsushi Shimoyama Koichi Fukase...
A 14-kDa lectin, named tachylectin-3, was newly identified from hemocytes of the Japanese horseshoe crab, <i>Tachypleus tridentatus</i>. This lectin exhibited hemagglutinating activity against human A-type erythrocytes, but not B- and O-types erythrocytes animal including those sheep, rabbit, horse, bovine. The tachylectin-3 equivalent to that a previously tachylectin-2, with affinity for<i>N</i>-acetyl-d-glucosamine or<i>N</i>-acetyl-d-galactosamine. However, inhibited by these...
Neuroblastoma (NBL), derived from the sympathetic precursor cells, is one of most common pediatric solid tumors. The expression N ‐acetylglucosaminyltransferase V and IX (GnT‐V GnT‐IX) mRNA in 126 primary NBLs were quantitatively analyzed higher levels GnT‐V found to be associated with favorable stages (1, 2 4s). Conversely, downregulation by small interfering RNA resulted a decrease susceptibility cell apoptosis induced retinoic acid NBL cells accompanied morphological change. These results...
For successful human placentation, invasion of trophoblast cells into the uterus and its associated vasculature is essential, regulation this process controlled by many factors at fetal-maternal interface. N-acetylglucosaminyltransferase V (GnT-V) a key enzyme that catalyzes β1, 6-N-acetylglucosamine (β1-6GlcNAc) branching on asparagine-linked oligosaccharides cell proteins. GnT-V product, β1-6GlcNAc, are known to regulate cellular transformation correlate with metastatic potential various...
Alteration of glycosphingolipid (GSL) expression plays key roles in the pathogenesis and pathophysiology many important human diseases, including cancer, diabetes glycosphingolipidosis. Inflammatory processes are involved development progression diabetic nephropathy, a major complication type 2 mellitus. GSLs known to play inflammatory responses various levels renal elevated mouse models nephropathy; however, little is regarding pathophysiological role these this disease process. We studied...
Both LARGE1 (formerly LARGE) and its paralog LARGE2 are bifunctional glycosyltransferases with xylosy- glucuronyltransferase activities, capable of synthesizing polymers composed a repeating disaccharide [-3Xylα1,3GlcAβ1-]. Post-translational modification the O-mannosyl glycan α-dystroglycan (α-DG) polysaccharide is essential for it to act as receptor ligands in extracellular matrix (ECM), both LARGE paralogs contribute vivo. have different tissue distribution profiles enzymatic properties;...
Bisubstrate-type inhibitors for N-acetylglucosaminyltransferase (GnT)-V and -IX were designed synthesized. These compounds carry both an acceptor trisaccaride UDP-GlcNAc component tethered by a linker of variable length. The trisaccharide unit was constructed using combination polymer support resin capture-release strategy. Namely, starting with beta-mannoside bound to low molecular weight monomethyl PEG (MPEG), successive glycosylations donors having chloroacetyl group produced the...
GM3, a precursor for synthesis of a- and b-series gangliosides, is elevated in adipocytes obese model animals sera human patients with type 2 diabetes and/or dyslipidemia. GM3 synthase (GM3S)-KO C57BL/6 mice display enhanced insulin sensitivity reduced development high-fat diet-induced resistance. However, the pathophysiological roles related gangliosides central control feeding metabolism remain unclear. We found that mouse (KKAy GM3S KO) generated by KO gene yellow strain, KKAy, displayed...
Intestinal cholesterol absorption is a key regulator of systemic homeostasis. Excessive dietary and its intestinal uptake lead to hypercholesterolemia, major risk factor for cardiovascular disease. mediated by Niemann-Pick C1-like 1 (NPC1L1), transmembrane protein localized in membrane microdomains (lipid rafts) enriched gangliosides cholesterol. The roles gangliosides, such as monosialodihexosylganglioside (GM3) synthesizing enzyme GM3 synthase (GM3S), NPC1L1-dependent have not been...