Molecular Biological Approach to Functions of Telencephalin, a Cell Adhesion Molecule and HNK-1 Carbohydrate Epitope, Which Is Commonly Expressed on Cell Adhesion Molecules in the Nervous System

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  • 神経系における細胞接着分子とこれに特異的に発現する糖鎖の分子生物学的研究
  • シンケイケイ ニ オケル サイボウ セッチャク ブンシ ト コレ ニ トクイテ

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Abstract

Cell surface carbohydrates modulate a variety of cellular functions, including recognition and adhesion. The HNK-1 carbohydrate epitope, which is recognized by the monoclonal antibody HNK-1, is specifically expressed on a series of cell adhesion molecules and also on some glycolipids in the nervous system over a wide range of species from insect to mammal. The HNK-1 epitope is spatially and temporally regulated during the development of the nervous system and associated with neural crest cell migration, neuron to glial cell adhesion, outgrowth of astrocytic processes and migration of cell body, as well as the preferential outgrowth of neurites from motor neurons. These observations together with the unusual chemical nature of the HNK-1 epitope, namely a non-reducing terminal 3-sulfoglucuronic acid residue, prompted us to study the biosynthesis of the HNK-1 epitope, in which a unique glucuronyltransferase (s) plays a key role. We found that the respective glucuronyltransferases are involved in the biosynthesis of the HNK-1 epitope on glycoproteins (GlcAT-P) and on glycolipids (GlcAT-L). Then, we isolated a novel glucuronyltransferase (GlcAT-P) specific for glycoprotein substrates and its cDNA from the rat brain. The primary structure deduced from the cDNA sequence predicted a type II transmenbrane protein with 347 amino acids. Transfection of the GlcAT-P cDNA into COS-1 cells induced not only expression of the HNK-1 epitope on the cell surface but also marked morphological changes of the cells, suggesting that the HNK-1 epitope was associated with the cell-substratum interaction. The GlcAT-P cDNA obtained in this study will be a useful molecular tool to open the way for further steps in the elucidation of the biological function of the HNK-1 carbohydrate epitope in the development of the nervous system.

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 118 (10), 431-446, 1998

    The Pharmaceutical Society of Japan

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