Chihiro Sato 교수

Sialic acids (Sia) are involved in many biological activities and frequently exist as monosialyl residues at the non-reducing terminal end of glycoconjugates. Occasionally, polymerized structures in the form of disialic acid (diSia), oligosialic acid (oligoSia) and polysialic acid (polySia) are also found in glycoconjugates. In particular, polySia, which is an evolutionarily conserved epitope from sea urchin to humans, is one of the most biologically important glycotopes in vertebrates. The biol

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 mutati

The pre-existence of alpha2-->8-linked disialic acid (di-Sia) and oligosialic acid (oligo-Sia) structures with up to 7 Sia residues was shown to occur on a large number of brain glycoproteins, including neural cell adhesion molecules (N-CAMs), by two highly sensitive chemical methods (Sato, C., Inoue, S., Matsuda, T., and Kitajima, K. (1998) Anal. Biochem. 261, 191-197; Sato, C., Inoue, S., Matsuda, T., and Kitajima, K. (1999) Anal. Biochem. 266, 102-109). This unexpected finding was also confir

Recently, we have shown that alpha 2,8-linked disialic acid (diSia) residue occurs in glycoproteins more frequently than ever recognized (Sato, C., Fukuoka, H., Ohta, K., Matsuda, T., Koshino, R., Kobayashi K., Troy, F. A., II, and Kitajima, K. (2000) J. Biol. Chem. 275, 15422--15431). In the course of identification of the diSia-containing glycoproteins in mammals, the 30-kDa glycoprotein was found in bovine serum. The 30-kDa glycoprotein was shown to be the bovine adipo Q, an adipocyte-specifi

alpha 2-->8-Linked polysialic acid (polySia) chains terminate O-linked oligosaccharide chains on Salmonidae fish egg polysialoglycoproteins (PSGPs). Expression of these surface PSGPs are developmentally regulated and the polySia epitope is functionally implicated in a number of distinct species-specific cell-cell recognition events during fertilization and early embryogenesis. To better understand the functional diversity of these PSGPs, structural studies of the polySia chains isolated from thr

Polysialic acid (polySia, PSA) is a unique constituent of the glycocalyx on the surface of bacterial and vertebrate cells. In vertebrates, its biosynthesis is highly regulated, not only in quantity and quality, but also in time and location, which allows polySia to be involved in various important biological phenomena. Therefore, impairments in the expression and structure of polySia sometimes relate to diseases, such as schizophrenia, bipolar disorder, and cancer. Some bacteria express polySia

We previously demonstrated that alpha2,8-linked disialic acid (diSia) residues occur in several glycoproteins of mammalian brains (Sato, C., Fukuoka, H., Ohta, K., Matsuda, T., Koshino, R., Kobayashi, K., Troy, F. A., II, and Kitajima, K. (2000) J. Biol. Chem. 275, 15422-15431). The role of the diSia epitope on these glycoproteins is not known, whereas the importance of the diSia epitope on glycolipids is well documented in neurite formation. In this study, we demonstrated that the diSia epitope

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 rhyt

The monoclonal antibody mAb.A2B5 is a marker for the detection of oligodendrocyte progenitor cells that differentiate into type-2 astrocytes and oligodendrocytes. It is also a useful antibody for separating these cells from other lineage populations. The epitope of this antibody is considered to be the gangliosides GT3 and GQ1c. In this study, we sought to define more precisely the structure of the epitope. Accordingly, we chemically synthesized defined oligosialic acid structures linked to phos

Sialic acid (Sia)-binding immunoglobulin-like lectin 7 (Siglec-7) is an inhibitory receptor primarily expressed on natural killer (NK) cells and monocytes. Siglec-7 is known to negatively regulate the innate immune system through Sia binding to distinguish self and nonself; however, a counter-receptor bearing its natural ligand remains largely unclear. Here, we identified a counter-receptor of Siglec-7 using K562 hematopoietic carcinoma cells presenting cell surface ligands for Siglec-7. We affi

糖鎖末端には通常1残基のシアル酸が存在するが、そのシアル酸残基の上にさらに数残基のシアル酸が直鎖状に縮重合してシアル酸重合体を形成する場合がある。α2→8結合ジシアル酸 (重合度DP=2) 構造はガングリオシドの構成成分としてよく知られており、細胞接着、細胞分化、シグナル伝達、時期特異的発現など、多くの生物学的機能を果たしている。また重合度が8以上のポリシアル酸構造は神経細胞接着分子上に存在しており、発生や分化に関わることが知られている。しかし、重合度が2から7程度のジ・オリゴシアル酸構造をもつ糖タンパク質の存在や機能についてはこれまでほとんど注目されて来なかった。しかし近年、ジ・オリゴ・ポリシアル酸 (シアル酸重合体) 構造を微量検出する手法が改良され、天然にジ・オリゴ・ポリシアル酸含有糖タンパク質がこれまで知られている以上に数多く存在することが明らかにされてきている。そのため糖タンパク質上のシアル酸重合体構造が、既にガングリオシドにおいて明らかにされてきた機能の一端を担う可能性が、また従来考えられてきたこととは全く異なる新たな機能を担っていること、さらには新たなポリシアル酸の機能が

α2→8結合ジシアル酸 (diSia) やオリゴシアル酸(oligoSia)(DP=2,3) 構造はガングリオシドの構成成分としてよく知られており、細胞接着、細胞分化、シグナル伝達、時期特異的発現など、多くの生物学的機能を果たしている。一方、そのような短いシアル酸オリゴマーを持つ糖タンパク質の存在や機能についてはこれまでほとんど注目されて来なかった。しかし近年、diSia や oligoSia 構造を微量検出する手法が改良され、天然にはdiSiaおよび oligoSia 含有糖タンパク質がこれまで知られている以上に数多く存在することが明らかにされてきている。そのため糖タンパク質上のdiSiaやoligoSia構造が、既にガングリオシドにおいて明らかにされているような機能を担う可能性が考えられる。この総説ではジシアル酸やオリゴシアル酸の分析法、存在分布、機能、生合成経路における最近の知見を述べる。