Sugar Chains: Decoding the Functions of Glycans


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BIOMEDICAL IMPORTANCE

Glycobiology 24, — The extended complete core M3 structure is novel and has recently been revealed bottom structure in Fig.

Sugar Chains - Decoding the Functions of Glycans | Tadashi Suzuki | Springer

The addition of a phosphate to the monosaccharide of glycans is a glycan modification whose significance is partially understood. For example, Man 6-phosphate acts as a recognition marker of lysosomal enzymes.

Overview of Glycobiology

Ribitol Rbo is a sugar alcohol, and the usage of Rbo or Rbo5P as a glycan component has not been reported in mammals. However, Rbo5P is used as a component of the teichoic acids present in the cell walls of most gram-positive bacteria. Cell Rep. Proteomics 15, — Thus, IIH6 was considered to recognize laminin-binding epitopes on sugar chains. Science , 88— Science , 93— A series of O -Man glycans with heterogeneous Man-core and peripheral structures is present in mammals.

The identification and characterization of enzymes involved in the biosynthesis of mammalian O -Man glycans are necessary to elucidate the function and regulation of the glycans. Glycobiology 20, — Cell 1, — FEBS Lett. On the other hand, the core M3 structure is synthesized in the ER Fig.

Research Group

Science , — Genes Cells 22, — Each glycosyltransferase responsible for synthesizing the extended complete core M3 structure has been identified Fig. Glycobiology 23, — Glycobiology 26, — Muscular dystrophies are genetic diseases that cause progressive muscle weakness and wasting. The best known and most common type of muscular dystrophy is Duchenne-type muscular dystrophy, and its causative gene, dystrophin , was identified in Dystrophin encodes an actin-binding cytoskeletal protein that is present inside the muscle membrane and is similar to spectrin.

Later, many proteins, including glycoproteins, form a large complex called DGC. The function of DGC is thought to connect extracellular matrix components and intracellular components with the actin cytoskeleton.

Research and Education

Notably, several components of the DGC have been identified as causative agents for different type muscular dystrophies. Neurology 84, — MEB and WWS are congenital muscular dystrophies characterized by brain malformations and structural abnormalities in the eye. Nature , — Brain , — The entire structure of the core M3 glycan and its biosynthetic pathway have been identified. We are trying to understand various biological phenomena operating this system at a molecular level, with a great emphasis on the glycans and lipids, rather neglected classes of molecule in cells.

Through our research activities, we would like to develop a diagnosis at super-early stage of disease as our goal on human health. We hope to achieve this goal with mighty young students. Glycosylation is one of such post-translational modifications, functional understanding of which is regarded as next major challenge in the life science at the post-genomic era.

To cope with this, we are bound to decode the biological information encoded and hidden in the sugar chains. Cellular lipids also function in cells with rather loose link with genomic information. These observations have led to the novel strategy of "Sugar Remodeling", where the regulation of glycosyltransferase gene expression could be used to characterize novel functions of glycans.

Glycan microarrays for decoding the glycome

Our major focus is to identify the target protein molecules of glycosyltransferases, as this will allow us to investigate the functions played by the glycosylation of the target protein. This would in turn improve our understanding of disease pathogenesis and the development of therapeutic tools. It has been shown that core-fucosylation of the target protein strictly determines the function of the receptor e.


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The deletion of the Fut8 gene in mice causes severe growth retardation and early post-natal death Figure 1. The surviving knockout mice show emphysema-like pathological changes in the lung Figure 2. This has further consequences, as it weakens the downstream phosphorylation of Smad2, which is needed to suppress the gene expression of matrix metalloproteinases MMPs.

Sugar Chains: Decoding the Functions of Glycans Sugar Chains: Decoding the Functions of Glycans
Sugar Chains: Decoding the Functions of Glycans Sugar Chains: Decoding the Functions of Glycans
Sugar Chains: Decoding the Functions of Glycans Sugar Chains: Decoding the Functions of Glycans
Sugar Chains: Decoding the Functions of Glycans Sugar Chains: Decoding the Functions of Glycans
Sugar Chains: Decoding the Functions of Glycans Sugar Chains: Decoding the Functions of Glycans
Sugar Chains: Decoding the Functions of Glycans Sugar Chains: Decoding the Functions of Glycans

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