NEUROBIOLOGY OF SULFATED GLUCURONYL GLYCOCONJUGATE

这个项目的主要目标是研究这种化学物质

The major goal of this project is to investigate the chemical structure, histological and topographical localization, biosynthesis and regulation of expression of the noval sulfated glucuronyl glycolipids (SGGL) in the developing nervous system. These glycolipid antigens are stage specific and developmentally regulated in the central nervous system during the important period of cell differentiation and cell migration. The SGG epitope is recognized by monoclonal antibody HNK-1, raised to surface antigens on human natural killer cells. SGG epitope is also expressed on a group of glycoproteins involved in cell-cell interaction such as, neural cell adhesion molecules (N-CAMs), myelin associated glycoprotein (MAG), and extra-cellular matrix proteins, ependymins. The proper development of the nervous system depends upon these molecules which are possibly involved in cell division, cell migration and for specific afferent and afferent connections. Studies are planned to determine the precise structure of these glycolipids with respect to nature of the carbohydrate, fatty acid, sphingosine base and glycosidic linkages. Sensitive quantitative assay of the glycolipids will be developed by using immunochemical, HPLC, and HPLC-mass spectrometric techniques. Developmental expression of these glycolipids in the different areas of the CNS will be studied. Expression in various species and neurological mutants will be investigated. The cellular and sub-cellular localization of SGGL during embryonic development of the rat nervous system will be studied by chemical and immunochemical methods. Biosynthesis of the SGGL will be investigated by charaterizing the various glycosyl transferases. Regulation of SGGL expression during development will be studied by determining the expression of the various glycosyl transferases and hydrolases. These basic studies will lay the foundation for the future work on the functional role of the SGG epitope on the glycolipids and glycoproteins.