研究者詳細 - 佐藤　ちひろ

Sialome analysis of the cephalochordate <i>Branchiostoma belcheri</i>, a key organism for vertebrate evolution Open Access

Impact of structural aberrancy of polysialic acid and its synthetic enzyme ST8SIA2 in schizophrenia. Open Access

Sato C, Kitajima K

Frontiers in cellular neuroscience 7 巻 ( APR ) 頁： 61 2013年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers in Cellular Neuroscience

Psychiatric disorders are a group of human diseases that impair higher cognitive functions. Whole-genomic analyses have recently identified susceptibility genes for several psychiatric disorders, including schizophrenia. Among the genes reported to be involved in psychiatric disorders, a gene encoding a polysialyltransferase involved in the biosynthesis of polysialic acid (polySia or PSA) on cell surfaces has attracted attention for its potential role in emotion, learning, memory, circadian rhythm, and behaviors. PolySia is a unique polymer that spatio-temporally modifies neural cell adhesion molecule (NCAM) and is predominantly found in embryonic brains, although it persists in areas of the adult brain where neural plasticity, remodeling of neural connections, or neural generation is ongoing, such as the hippocampus, subventricular zone, thalamus, prefrontal cortex, and amygdala. PolySia is thought to be involved in the regulation of cell-cell interactions; however, recent evidence suggests that it is also involved in the functional regulation of ion channels and neurologically active molecules, such as BDNF, FGF2, and dopamine that are deeply involved in psychiatric disorders. In this review, the possible involvement of polysialyltransferase (ST8SIA2/ST8SiaII/STX/Siat8B) and its enzymatic product, polySia, in schizophrenia is discussed. © 2013 Sato and Kitajima.

DOI： 10.3389/fncel.2013.00061

Sato, C

SIALOBIOLOGY: BIOSYNTHESIS, STRUCTURE AND FUNCTION: SIALIC ACID GLYCOCONJUGATES IN HEALTH AND DISEASE 頁： 33 - 75 2013年

ポリシアル酸による神経機能の調節. 実験医学 31巻 10号 (増刊) pp. 26-33; 第三の生命鎖査読有り

佐藤ちひろ

実験医学 31 巻頁： 26 - 33 2013年

Guérardel, Y; Chang, LY; Fujita, A; Coddeville, B; Maes, E; Sato, C; Harduin-Lepers, A; Kubokawa, K; Kitajima, K

GLYCOBIOLOGY 22 巻 ( 4 ) 頁： 479 - 491 2012年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Glycobiology

Sialic acid, a common terminal substitution of glycoconjugates, has been so far consistently identified in all vertebrates as well as in a growing number of bacterial species. It is assumed to be widely distributed among animal species of the deuterostome phylum, based on its identification in few echinoderm and all vertebrate species. However, whole sections of deuterostome, especially those intermediate species between invertebrates and vertebrates including cephalochordates, urochordates and hemichordates, are still unexplored in term of sialylation capacities. The discovery of functional sialic acid machinery in some of these species may shed new light onto the evolution of glycosylation capacities in deuterostome lineage. In a first approach, we investigated the sialylation pattern of a cephalocordate species, Branchiostoma belcheri, which occupies a strategic phylogenetic position to understand the transition of invertebrates toward vertebrates. Structural analysis of B. belcheri glycoconjugates established that this organism synthesizes large quantities of various sialic acids, some of which present rare or novel structures such as methylated sialic acids. These sialic acids were shown to be mainly associated with mono-and disialylated core 1-type O-glycans. Moreover, screening of the animal organs revealed the existence of exquisite tissue specificity in the distribution of sialic acids. Description of sialylation profiles was then correlated with the expression patterns of key enzymes involved in the biosynthesis of major forms of sialic acids, which provides the first complete overview of the sialylation patterns in cephalochordates. © 2011 The Author.

DOI： 10.1093/glycob/cwr155

Structural and functional impairments of polysialic acid (polySia)-neural cell adhesion molecule (NCAM) synthesized by a mutated polysialyltransferase of a schizophrenic patient Open Access

Hane, M; Sumida, M; Kitajima, K; Sato, C

PURE AND APPLIED CHEMISTRY 84 巻 ( 9 ) 頁： 1895 - 1906 2012年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Pure and Applied Chemistry

Polysialic acid (polySia) is a homopolymer of sialic acid with a degree of polymerization (DP) of 8-100. When present on neural cell adhesion molecule (NCAM), polySia has anti-adhesive effects on cell-cell interactions owing to its bulky polyanionic nature, and is involved in the regulation of neurogenesis and neuronal functions. Recently, we demonstrated that polySia functions not only as an anti-cell adhesion molecule, but also as a reservoir scaffold for brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF2), which are biologically active molecules in neurogenesis. To understand the significance of polySia structure in the reservoir function, we focused on polySia-NCAM biosynthesized by mutated polysialyltransferase (ST8SiaII or STX) that was reported in a schizophrenia patient. The polySia-NCAM biosynthesized by mutant ST8SiaII/STX contained less polySia with shorter chain length and exhibited impaired reservoir function for BDNF and FGF2 as compared with that synthesized by wild-type (wt) ST8SiaII/STX. Our findings suggest that the quantity and quality of polySia on NCAM are important for normal neuronal functioning. © 2012 IU PAC.

DOI： 10.1351/PAC-CON-11-12-10

Co-expression of two distinct polysialic acids, α2,8- and α2,9-linked polymers of N-acetylneuraminic acid, in distinct glycoproteins and glycolipids in sea urchin sperm. Open Access

CiNii Research

Miyata S, Yamakawa N, Toriyama M, Sato C, Kitajima K

Glycobiology 21 巻 ( 12 ) 頁： 1596 - 605 2011年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Glycobiology

Naturally occurring polysialic acid (polySia) structures have a large diversity, primarily arising from the diversity in the sialic acid components as well as in the intersialyl linkages. In 2004, we demonstrated the presence of a new type of polySia, 8-O-sulfated N-acetylneuraminic acid (Neu5Ac) capped α2,9-linked polyNeu5Ac, on the O-glycans of a major 40-80 kDa sialoglycoprotein, flagellasialin, in sea urchin sperm. In this study, we demonstrated that another type of polySia, the α2,8-linked polyNeu5Ac, exclusively occurs on O-glycans of a 190 kDa glycoprotein (190 kDa-gp), whereas the α2,9-linked polyNeu5Ac is exclusively present on flagellasialin. The 190 kDa-gp is localized in both flagellum and head of sperm. We also demonstrated that polysialogangliosides containing the α2,8-linked polyNeu5Ac are present in sperm head. Thus, this study shows two novel features of the occurrence of polySia in nature, the co-localization of polySia with different intersialyl linkages, the α2,8-and α2,9-linkages, in a single cell and the occurrence of α2,8-linked polyNeu5Ac in glycolipids. Anti-α2,8-linked polyNeu5Ac antibody had no effect on fertilization, which contrasted with the previous results that anti-α2,9-linked polyNeu5Ac antibody inhibited sperm motility and fertilization. Based on these properties, distinct functions of α2,8-and α2,9-polySia structures are implicated in fertilization. © 2011 The Author.

DOI： 10.1093/glycob/cwr081

Structural and functional impairments of polysialic acid by a mutated polysialyltransferase found in schizophrenia. Open Access

New Functions of Polysialic Acid and Its Relationship to Schizophrenia Open Access

Sato, C; Kitajima, K

TRENDS IN GLYCOSCIENCE AND GLYCOTECHNOLOGY 23 巻 ( 133 ) 頁： 221 - 238 2011年9月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Trends in Glycoscience and Glycotechnology

Polysialic acid (polySia), particularly α2,8-linked polyNeu5Ac (DP=8~400), is a unique polymer that spatiotemporally modifies neural cell adhesion molecule (NCAM), predominantly in embryonic brains. PolySia is considered to function as a negative regulator of adhesion between cells, and between cells and extracellular matrix due to its extremely polyanionic nature and steric hindrance. Through its antiadhesive property and spatio-temporal expression, polySia is involved in cell migration, neural outgrowth, axonal guidance, synaptic plasticity, and the development of normal neural circuits and neurogenesis. Due to improvements of polySiadetection methods, it has been shown that polySia expression persists in the hippocampus and olfactory bulb of adults, where neurogenesis is ongoing; however, the functions of polySia, particularly in adult brains, remain incompletely resolved. Recently, we demonstrated that polySia functions not only as an anti-adhesive molecule, but also as a reservoir for specific bioactive molecules, such as neurotrophic factors, neurotransmitters, and growth factors, which regulate neural function. In addition, studies have revealed that the enzymatic activity of STX, which is involved in the synthesis of polySia, derived from schizophrenic patient is low and that the product of the enzyme, polySia on NCAM is impaired with respect to both quantity and quality. Notably, impaired polySia-NCAM cannot effectively retain bioactive molecules, including BDNF, dopamine, and FGF2. Taken together, the impairment of polySia might influence the retention function of polySia and lead to the development of psychiatric disorders, such as schizophrenia, which are reported to express either lower or elevated amounts of polySia compared with normal brains. ©2011 FCCA.

DOI： 10.4052/tigg.23.221

Isomura R, Kitajima K, Sato C

The Journal of biological chemistry 286 巻 ( 24 ) 頁： 21535 - 45 2011年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Biological Chemistry

Polysialic acid (polySia), a unique acidic glycan modifying neural cell adhesion molecule (NCAM), is known to regulate embryonic neural development and adult brain functions. Polysialyltransferase STX is responsible for the synthesis of polySia, and two single nucleotide polymorphisms (SNPs) of the coding region of STX are reported from schizophrenic patients: SNP7 and SNP9, respectively, giving STX(G421A) with E141K and STX(C621G) with silent mutations. In this study, we focused on these mutations and a binding activity of polySia to neural materials, such as brain-derived neurotrophic factor (BDNF). Here we describe three new findings. First, STX(G421A) shows a dramatic decrease in polySia synthetic activity on NCAM, whereas STX(C621G) does not. The STX(G421A)-derived polySia-NCAM contains a lower amount of polySia with a shorter chain length. Second, polySia shows a dopamine (DA) binding activity, which is a new function of polySia as revealed by frontal affinity chromatography for measuring the polySia-neurotransmitter interactions. Interestingly, the STX(G421A)-derived polySia-NCAM completely loses the DA binding activity, whereas it greatly diminishes but does not lose the BDNF binding activity. Third, an impairment of the polySia structure with an endosialidase modulates the DA-mediated Akt signaling. Taken together, impairment of the amount and quality of polySia may be involved in psychiatric disorders through impaired binding to BDNF and DA, which are deeply involved in schizophrenia and other psychiatric disorders, such as depression and bipolar disorder. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

DOI： 10.1074/jbc.M111.221143

IgG2 dominancy and carbohydrate recognition specificity of C3H/He mouse antibodies directed to cross-reactive carbohydrate determinants (CCDs) bearing beta-(1,2)-xylose and alpha-(1,3)-fucose.

Hino S, Umeda F, Inumaru S, Aoki N, Sato C, Okajima T, Nadano D, Matsuda T

Immunology letters 133 巻 ( 1 ) 頁： 28 - 34 2010年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Immunology Letters

Few common carbohydrate epitopes consisting of terminal β-(1,2)-xylose and/or α-(1,3)-fucose residues are shared by a variety of glycoproteins from plants, insects and parasitic worms, termed cross-reactive carbohydrate determinant (CCD), and frequently recognized by IgE antibodies of patients with food and/or respiratory allergy, though clinical relevancy of such CCD-specific IgE is still controversial. Attention has also been focused on CCDs from the undesired post-translational modification of recombinant therapeutic proteins produced by transgenic plants and insects. In the present study, to clarify immunogenic potentials of CCD-bearing glycoproteins, the antibody response to a model plant glycoprotein, horseradish peroxidase (HRP) was investigated in a mouse model. C3H/He mice were immunized with HRP plus Al(OH)<inf>3</inf> or Freund's adjuvant, and IgG and IgE responses to CCDs in addition to HRP were analyzed by ELISA using some distinct glycoproteins with known N-glycan structures. IgE response to HRP was induced remarkably, whereas that to CCD was weaker and delayed. Moreover, apparent ratio of the CCD-specific antibodies to HRP-specific ones tended to be higher in IgG2a and IgG2b isotypes than IgG1, IgG3 and IgE. In contrast to rabbit antibodies, the CCD-specific antibodies from the mice gave poor reactivity with bromelain and honeybee phospholipase A2, suggesting the critical role of both β-(1,2)-xylose and α-(1,3)-mannose in the CCD-recognition by the mouse antibodies. Moreover, the mouse antibodies showed weaker cross-reactivity to pollen- and insect-derived glycoproteins than the rabbit ones. Thus, in this mouse model, not only IgE but also IgG2 antibody responses to CCDs were induced by immunizing with a CCD-bearing glycoprotein, suggesting that CCDs affected not only Th2-type but also Th1-type antibody response at least in C3H/He mice. © 2010 Elsevier B.V.

DOI： 10.1016/j.imlet.2010.06.007

Extensive enrichment of N-glycolylneuraminic acid in extracellular sialoglycoproteins abundantly synthesized and secreted by human cancer cells.

Inoue S, Sato C, Kitajima K

Glycobiology 20 巻 ( 6 ) 頁： 752 - 62 2010年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Glycobiology

N-Glycolylneuraminic acid (Neu5Gc) is the second most populous sialic acid (Sia). The only known biosynthetic pathway of Neu5Gc is the hydroxylation of cytidine-5′monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), catalyzed by CMP-Neu5Ac hydroxylase (CMAH). Neu5Gc is abundantly found in mammals except for human, in which CMAH is inactivated due to mutation in the CMAH gene. Evidence has accumulated to show occurrence of Neu5Gc-containing glycoconjugates in sera of cancer patients, human cancerous tissues and cultured human cell lines. Recently, occurrence of natural antibodies against Neu5Gc was shown in healthy humans and is a serious problem for clinical xenotransplantation and stem cell therapies. Studying human occurrence of Neu5Gc is of importance and interest in a broad area of medical sciences. In this study, using a fluorometric high performance liquid chromatography method, we performed quantitative analyses of Sias both inside and in the external environment of the cell and found that (i) incorporation of Neu5Gc was most prominent in soluble glycoproteins found both in the extracellular space and inside the cell as the major Sia compounds. (ii) Of the total Neu5Gc in the Sia compounds that the cells synthesized, 90% was found in the secreted sialoglycoproteins, whereas for Neu5Ac, 70% was found in the secreted sialoglycoproteins. (iii) The Neu5Gc ratio was higher in the secreted sialoglycoproteins (as high as 40% of total Sias) than in intracellular sialoglycoproteins. (iv) The majority of the secreted sialoglycoproteins was anchored on the culture dishes and solubilized by brief trypsin treatment. Based on these findings, a new idea on the mechanism of accumulation of Neu5Gc in cancer cells was proposed. © The Author 2010. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

DOI： 10.1093/glycob/cwq030