Kazuhiro Aoki

Kazuhiro Aoki
University of Georgia | UGA · Complex Carbohydrate Research Center

About

88
Publications
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Publications

Publications (88)
Article
Full-text available
Mucins are large gel-forming polymers inside the mucus barrier that inhibit the yeast-to-hyphal transition of Candida albicans, a key virulence trait of this important human fungal pathogen. However, the molecular motifs in mucins that inhibit filamentation remain unclear despite their potential for therapeutic interventions. Here, we determined th...
Article
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Alzheimer’s disease (AD) is characterized by accumulation of misfolded proteins. Genetic studies implicate microglia, brain-resident phagocytic immune cells, in AD pathogenesis. As positive effectors, microglia clear toxic proteins, whereas as negative effectors they release proinflammatory mediators. An imbalance of these functions contributes to...
Article
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Recent advances in carbohydrate chemistry, chemical biology, and mass spectrometric techniques have opened the door to rapid progress in uncovering the function and diversity of glycan structures associated with human health and disease. These strategies can be equally well applied to advance non-human health care research. To date, the glycomes of...
Article
Fabry disease results from a deficiency of the lysosomal enzyme ⍺‐Galactosidase‐A (⍺‐Gal A) and is estimated to occur in approximately 1:4100 live births. Characteristic of the disease is the accumulation of α‐Gal‐A substrates, primarily the glycosphingolipids (GSLs) globotriaosylceramide and globotriaosylsphingosine. Thrombotic events are a signif...
Preprint
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GM3 Synthase Deficiency (GM3SD) is a neurodevelopmental disorder resulting from pathogenic variants in the ST3GAL5 gene, which encodes GM3 synthase, a glycosphingolipid (GSL)-specific sialyltransferase. This enzyme adds a single alpha3-linked sialic acid to the terminal galactose of lactosylceramide (LacCer) to produce the monosialylated gangliosid...
Article
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Mucus barriers accommodate trillions of microorganisms throughout the human body while preventing pathogenic colonization1. In the oral cavity, saliva containing the mucins MUC5B and MUC7 forms a pellicle that coats the soft tissue and teeth to prevent infection by oral pathogens, such as Streptococcus mutans2. Salivary mucin can interact directly...
Article
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Plasmin is the key enzyme in fibrinolysis. Upon interaction with plasminogen activators, the zymogen plasminogen is converted to active plasmin. Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor...
Article
Glycans are one of the fundamental classes of macromolecules and are involved in a broad range of biological phenomena. A large variety of glycan structures can be synthesized depending on tissue or cell types and environmental changes. Here, we developed a comprehensive glycosylation mapping tool, termed GlycoMaple, to visualize and estimate glyca...
Article
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This protocol describes an integrated approach for analyzing site-specific N- and O-linked glycosylation of SARS-CoV-2 spike protein by mass spectrometry. Glycoproteomics analyzes intact glycopeptides to examine site-specific microheterogeneity of glycoproteins. Glycomics provides structural characterization on any glycan assignments by glycoproteo...
Article
Background The immunoinhibitory receptor Siglec-8 on the surface of human eosinophils and mast cells binds to sialic acid-containing ligands in the local milieu resulting in eosinophil apoptosis, inhibition of mast cell degranulation and suppression of inflammation. Siglec-8 ligands were found on postmortem human trachea and bronchi and on upper ai...
Article
The SARS-CoV-2 betacoronavirus uses its highly glycosylated trimeric Spike protein to bind to the cell surface receptor angiotensin converting enzyme 2 (ACE2) glycoprotein and facilitate host cell entry. We utilized glycomics-informed glycoproteomics to characterize site-specific microheterogeneity of glycosylation for a recombinant trimer Spike mi...
Article
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A fraction of sperm deposited at mating or insemination reaches the oviduct isthmus where sperm are retained and thereby form a reservoir. This reservoir delays capacitation, prevents polyspermy, selects a fertile population of sperm, and, foremost, increases sperm lifespan. The molecular interactions underlying the formation of a sperm reservoir a...
Article
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Fabry disease is an X-linked lysosomal storage disease caused by deficiency of α-galactosidase A. Ocular findings, such as cornea verticillata, cataracts, and retinal vascular tortuosity, serve as important diagnostic markers. We aimed to evaluate ocular phenotypes in α-galactosidase A-deficient (Fabry) rats and hypothesized that these rats would m...
Article
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Background: Among Amish communities of North America, biallelic mutations of ST3GAL5 (c.694C > T) eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides. Systemic ganglioside deficiency is associated with infantile onset psychomotor retardation, slow brain growth, intractable epilepsy, deafness, and cortical visual i...
Article
Full-text available
Human siglecs are a family of 14 sialic acid binding proteins, most expressed on subsets of immune cells where they regulate immune responses. Siglec-8 is expressed selectively on human allergic inflammatory cells - primarily eosinophils and mast cells - where engagement causes eosinophil apoptosis and inhibits mast cell mediator release. Evidence...
Article
Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays. We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-s...
Article
Sialyltransferases are a family of 20 gene products in mice and humans that transfer sialic acid from its activated precursor, CMP-sialic acid, to the terminus of glycoprotein and glycolipid acceptors. ST3Gal-II (coded by the St3gal2 gene) transfers sialic acid preferentially to the 3-position of galactose on the Galβ1-3GalNAc terminus of gangliosi...
Article
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Environmental and metabolic processes shape the profile of glycoprotein glycans expressed by cells, whether in culture, developing tissues, or mature organisms. Quantitative characterization of glycomic changes associated with these conditions has been achieved historically by reductive coupling of oligosaccharides to various fluorophores following...
Article
Biomarkers capable of detecting and targeting epithelial ovarian cancer (EOC) cells for diagnostics and therapeutics would be extremely valuable. Ovarian cancer is the deadliest reproductive malignancy among women in the U.S. killing over 14,000 women each year. Both the lack of presenting symptoms and high mortality rates illustrate the need for e...
Article
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Separation of proteins by SDS-PAGE followed by in-gel proteolytic digestion of resolved protein bands has produced high-resolution proteomic analysis of biological samples. Similar approaches, that would allow in-depth analysis of the glycans carried by glycoproteins resolved by SDS-PAGE, require special considerations in order to maximize recovery...
Article
Most currently available glycan structure databases use their own proprietary structure representation schema and contain numerous annotation errors. These cause problems when glycan databases are used for the annotation or mining of data generated in the laboratory. Due to the complexity of glycan structures, curating these databases is often a te...
Article
Sensitive and specific biomarkers for pancreatic cancer are currently unavailable. The high mortality associated with adenocarcinoma of the pancreatic epithelium justifies the broadest possible search for new biomarkers that can facilitate early detection or monitor treatment efficacy. Protein glycosylation is altered in many cancers, leading many...
Article
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A game of tag: N-Glycans on the surface of living cells were selectively tagged by exogenously administering recombinant ST6Gal I sialyltransferase and azide-modified CMP-Neu5Ac. This modification was followed by a strain-promoted cycloaddition using a biotin-modified dibenzylcyclooctynol (red star=biotin). The methodology will make it possible to...
Article
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"Salt & Pepper" syndrome is an autosomal recessive condition characterized by severe intellectual disability, epilepsy, scoliosis, choreoathetosis, dysmorphic facial features, and altered dermal pigmentation. High density SNP array analysis performed on siblings first described with this syndrome detected 4 shared regions of loss of heterozygosity...
Article
SDS-PAGE is a widely used technique for protein separation and in-gel tryptic digestion of resolved protein bands has enhanced the resolution of protoeomic analysis. To augment this technology and expand its usefulness for glycoproteomics, we have developed and improved methods to release and recover O-linked glycans from proteins resolved in SDS-P...
Article
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The Golgi receives the entire output of newly synthesized cargo from the endoplasmic reticulum, processes it in the stack largely through modification of bound oligosaccharides, and sorts it in the trans-Golgi network. GRASP65 and GRASP55, two proteins localized to the Golgi stack and early secretory pathway, mediate processes including Golgi stack...
Article
Infection by Opisthorchis viverrini (liver fluke) is a major public health problem in southeastern Asia, resulting in hepatobiliary disease and cholangiocarcinoma. Fluke surface glycoconjugates are prominently presented to the host, thereby constituting a crucial immunological interface that can determine the parasite's success in establishing infe...
Article
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After mating, many female mammals store a subpopulation of sperm in the lower portion of the oviduct, forming a reservoir. The reservoir lengthens sperm lifespan, regulates sperm capacitation, controls polyspermy and selects normal sperm. It is believed that sperm bind to glycans on the oviduct epithelium to form the reservoir but the specific adhe...
Article
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The abundance and structural diversity of glycans on glycoproteins and glycolipids are highly regulated and play important roles during vertebrate development. Because of the challenges associated with studying glycan regulation in vertebrate embryos, we have chosen to study mouse embryonic stem (ES) cells as they differentiate into embryoid bodies...
Article
Upon semen deposition in the female reproductive tract, a fraction of the sperm is transported to the isthmus (lower oviduct) to form a functional sperm reservoir. This reservoir is involved in the regulation of sperm functions necessary for proper fertilization in a timely manner, given that insemination and ovulation are not always well synchroni...
Article
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Gangliosides—sialylated glycosphingolipids—are the major glycoconjugates of nerve cells. The same four structures—GM1, GD1a, GD1b and GT1b—comprise the great majority of gangliosides in mammalian brains. They share a common tetrasaccharide core (Galβ1–3GalNAcβ1-4Galβ1-4Glcβ1-1′Cer) with one or two sialic acids on the internal galactose and zero (GM...
Conference Paper
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Cell surface mucins configure the cell surface by presenting extended protein backbones that are heavily O-glycosylated. The glycopeptide structures establish physicochemical properties at the cell surface that enable and block the formation of biologically important molecular complexes. Some mucins, such as MUC1, associate with receptor tyrosine k...
Article
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Cryptococcal meningoencephalitis is an AIDS-defining illness caused by the opportunistic pathogen Cryptococcus neoformans. This organism possesses an elaborate polysaccharide capsule that is unique among pathogenic fungi, and the glycobiology of C. neoformans has been a focus of research in the field. The capsule and other cellular glycans and glyc...
Article
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Dystroglycanopathies are a subset of congenital muscular dystrophies wherein α-dystroglycan (α-DG) is hypoglycosylated. α-DG is an extensively O-glycosylated extracellular matrix-binding protein and a key component of the dystrophin-glycoprotein complex. Previous studies have shown α-DG to be post-translationally modified by both O-GalNAc- and O-ma...
Article
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Precise glycan structures on specific glycoproteins impart functionalities essential for neural development. However, mechanisms controlling embryonic neural-specific glycosylation are unknown. A genetic screen for relevant mutations in Drosophila generated the sugar-free frosting (sff) mutant that reveals a new function for protein kinases in regu...
Article
As glycan characterization methods increase in sensitivity, new opportunities arise to undertake glycomic analyses on limiting amounts of material. Developing systems present special challenges since the amount of available tissue can restrict deep glycan characterization. We have optimized mass spectrometric methods with the goal of obtaining full...
Article
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Addition of fucose (Fuc) to glycoprotein N-linked glycans or in O-linkage directly to Ser/Thr residues modulates specific cell–cell interactions and cell signaling events. Vertebrates and invertebrates add Fuc in α6-linkage to the reducing terminal N-acetylglucosamine residue of N-glycans. In Drosophila and other invertebrates, Fuc can also be adde...
Article
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The main extracellular matrix binding component of the dystrophin-glycoprotein complex, α-dystroglycan (α-DG), which was originally isolated from rabbit skeletal muscle, is an extensively O-glycosylated protein. Previous studies have shown α-DG to be modified by both O-GalNAc- and O-mannose-initiated glycan structures. O-Mannosylation, which accoun...
Article
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Robust quantification is an essential component of comparative -omic strategies. In this regard, glycomics lags behind proteomics. Although various isotope-tagging and direct quantification methods have recently enhanced comparative glycan analysis, a cell culture labeling strategy, that could provide for glycomics the advantages that SILAC provide...
Article
Polygalacturonase inhibiting proteins (PGIPs) are members of the leucine rich repeat family of proteins, involved in plant defense against fungal pathogens. PGIPs exhibit a remarkable degree of specificity in terms of their ability to bind and inhibit their target molecules, the endopolygalacturonases (EPGs). This specificity has been attributed fo...
Article
We isolated two major zwitterionic glycosphingolipids (ZGLs) from the phytopathogenic filamentous fungus Trichoderma viride. Structural analyses showed that the ZGLs (designated Tv-ZGL2 and Tv-ZGL3) were the same as the glycosphingolipids ZGL2 and ZGL4 from Acremonium sp., which are described in our previous paper. ZGLs have the following structure...