A5063773126- Glycosylation and Glycoproteins Research
- Muscle Physiology and Disorders
- Carbohydrate Chemistry and Synthesis
- Ubiquitin and proteasome pathways
- Lysosomal Storage Disorders Research
- Parathyroid Disorders and Treatments
- Genetic Syndromes and Imprinting
- Proteoglycans and glycosaminoglycans research
- Galectins and Cancer Biology
- Genetic and Kidney Cyst Diseases
- Cardiomyopathy and Myosin Studies
- Sirtuins and Resveratrol in Medicine
- Cell Adhesion Molecules Research
- Studies on Chitinases and Chitosanases
- Medical Imaging and Pathology Studies
- Endoplasmic Reticulum Stress and Disease
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Bone health and treatments
- Protease and Inhibitor Mechanisms
- Autophagy in Disease and Therapy
- Congenital heart defects research
- Cellular transport and secretion
- Genetic Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Parasitic Infections and Diagnostics
Tokyo Metropolitan Institute of Gerontology
2004-2024
Tokyo Metropolitan Geriatric Hospital
2011-2022
Kogakuin University
2009
Glycosylation is an essential post-translational modification that underlies many biological processes and diseases. α-dystroglycan (α-DG) a receptor for matrix synaptic proteins causes muscular dystrophy lissencephaly upon its abnormal glycosylation (α-dystroglycanopathies). Here we identify the glycan unit ribitol 5-phosphate (Rbo5P), phosphoric ester of pentose alcohol, in α-DG. Rbo5P forms tandem repeat functions as scaffold formation ligand-binding moiety. We show enzyme activities...
Significance Congenital muscular dystrophy (CMD) is caused by hypoglycosylation of α-dystroglycan (α-DG). In some CMD patients, mutations in the gene encoding protein O -linked mannose β1,2- N -acetylglucosaminyltransferase 1, POMGnT1 , are responsible for such hypoglycosylation. Many CMD-related genes thought to be involved glycosylation core M3, a specific -mannose–type structure α-DG. Although has long been known associated with CMD, its role M3 remains unclear. Our results reveal that...
A defect of protein O-mannosylation causes congenital muscular dystrophy with brain malformation and structural eye abnormalities, so-called Walker-Warburg syndrome. Protein is catalyzed by O-mannosyltransferase 1 (POMT1) its homologue, POMT2. Coexpression POMT1 POMT2 required to show activity. Here we have shown that forms a complex the possesses Results indicate associate physically functionally in vivo. Recently, three mutations were reported gene patients who showed milder phenotypes...
Alteration of glycoprotein glycans often changes various properties the target and contributes to a wide variety diseases. Here, we focused on N-glycans amyloid precursor protein whose cleaved fragment, beta-amyloid, is thought cause much pathology Alzheimer's disease (AD). We previously determined N-glycan structures normal mutant proteins (the Swedish type London type). In comparison with protein, had higher contents bisecting GlcNAc residues. Because N-acetylglucosaminyltransferase III...
Alterations of the structure and/or amount glycans present on proteins are associated with many diseases. We previously demonstrated that changes in N-glycans alter Aβ production. In study, we focused relationship between Alzheimer's disease (AD) and O-glycan, another type glycan. The UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family functions first step mucin-type O-glycan synthesis. Analysis expression GalNAc-Ts human brain using real-time PCR...
O-Mannosyl glycans are important in muscle and brain development. Protein O-mannosyltransferase (POMT) catalyzes the initial step of O-mannosyl glycan biosynthesis. To understand which serine (Ser) threonine (Thr) residues POMT recognizes for mannosylation, we prepared a series synthetic peptides based on mucin-like domain α-dystroglycan (α-DG), one best known O-mannosylated proteins mammals. In α-DG, spans amino acid 316 to 489. Two similar peptide sequences, corresponding 401–420 336–355,...
Journal Article Role of N-glycans in maintaining the activity protein O-mannosyltransferases POMT1 and POMT2 Get access Hiroshi Manya, Manya * 1Glycobiology Research Group, Tokyo Metropolitan Institute Gerontology, Foundation for on Aging Promotion Human Welfare, 35-2 Sakaecho, Itabashi-ku, 173-0015; 2Department Applied Chemistry, Kogakuin University, 163-8677, Japan *Hiroshi Manya. Glycobiology 173-0015, Japan, Tel: 81-3-3964-3241, Ext. 3055, Fax: 81-3-3579-4776, E-mail: manya@tmig.or.jp....
In sharp contrast with analysis of N-glycan that can be prepared by PNGase F, O-glycan remains challenging due to a lack versatile and simple procedures, especially those mediating cleavage O-glycans from proteins. Most N-glycans are modified sialic acids at the non-reducing end their glycosidic linkages labile, making it difficult measure glycans mass spectrometric analysis. addition, acid residues present on glycan chains via α2,3-, α2,6-, α2,8-linkages as structural isomers.
Sialic acid attached to nonreducing ends of glycan chains via different linkages is associated with specific interactions and physiological events. Linkage-specific derivatization sialic great interest for distinguishing acids by mass spectrometry, specifically events governed sialyl linkage types. In the present study, we demonstrate that α-2,3/8-sialyl linkage-specific amidation esterified sialyloligosaccharides can be achieved an intramolecular lactone. The method lactone-driven...
The α-Klotho mouse is an animal model that prematurely exhibits phenotypes resembling human aging owing to mutation of the gene. Although mice appear normal at birth, they begin showing multiple age-associated disorders after 3–4 weeks. Meanwhile, overexpression extends lifespan. Therefore, may be involved in process. protein has homology β-glucosidase and proposed have glycosidase activity. However, it unclear whether glycan alterations are present mice. Here we found increased levels...
Protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is a Golgi glycosyltransferase that catalyzes the formation of N-acetylglucosamine (GlcNAc) β1→2Man linkage O-mannosyl glycan. POMGNT1 not modified by N-glycans because there are no potential N-glycosylation sites; however, it clear whether O-glycans. To determine O-glycosylated, we prepared recombinant human from HEK293T cells. The was recognized Sambucus sieboldiana lectin (SSA), and sialidase digestion decreased SSA...
Glycans are involved in many fundamental cellular processes such as growth, differentiation, and morphogenesis. However, their broad structural diversity makes analysis difficult. Glycomics via mass spectrometry has focused on the composition of glycans, but informatics not kept pace with development instrumentation measurement techniques. We developed Toolbox Accelerating (TAG), which glycans can be added manually to glycan list that freely designed labels sialic acid modifications, fast...
The klotho mouse shows multiple phenotypes resembling human aging caused by the mutation of a single gene. This is insertion ectopic DNA into regulatory region α-klotho gene encodes type I membrane protein that expressed predominantly in kidney and brain. As result defect expression, exhibits age-associated disorders, such as arteriosclerosis, osteoporosis, pulmonary emphysema short life span. However, mechanism which product suppresses phenomena has not been identified. Analysis...
Abstract The deficiency of α-Klotho in mice causes phenotypes resembling human age-associated disorders at 3–4 weeks after birth and shows short lifespans ∼2 months. One the crucial symptoms is pulmonary emphysema, although not expressed lungs. secreted from kidneys probably involved pathology emphysema because kidney-specific knockout exhibit emphysematous structural changes. We examined whether any glycan changes mouse lungs were observed, reported to have glycosidase activity. Here, we...
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