NEUROBIOLOGY OF SULFATED GLUCURONYL GLYCOCONJUGATE

硫酸化葡萄糖醛酰糖复合物的神经生物学

• 批准号: 3408975
• 负责人: FIROZE B JUNGALWALA
• 金额: $ 16.97万
• 依托单位: EUNICE KENNEDY SHRIVER CTR MTL RETARDATN
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3408975
• 关键词: cell adhesion; cell cell interaction; cell cycle; cell differentiation; cell migration; developmental neurobiology; enzyme mechanism; extracellular matrix; glycolipids; high performance liquid chromatography; immunochemistry; laboratory mouse; laboratory rabbit; laboratory rat; lipid biosynthesis; lipid structure; mass spectrometry; monoclonal antibody; myelin glycoprotein; neural cell adhesion molecules; swine

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.

这个项目的主要目标是研究这种化学物质。 结构、组织学和地形学定位、生物合成 和对新的硫代葡萄糖醛酸基表达的调控 发育中神经系统中的糖脂(SGGL)。这些 糖脂抗原是阶段特异性的和发育的 在重要的中枢神经系统中调节 细胞分化和细胞迁移时期。SGG表位 被单抗HNK-1识别，浮出水面 人类自然杀伤细胞上的抗原。SGG表位也是 在一组与细胞-细胞有关的糖蛋白上表达 相互作用，如神经细胞黏附分子(N-CaM)， 髓鞘相关糖蛋白(MAG)和细胞外基质 蛋白质，室管膜蛋白。神经质的正常发育 系统依赖于这些可能涉及的分子 在细胞分裂、细胞迁移和特定的传入和 传入连接。计划进行研究，以确定 这些糖脂的精确结构与 碳水化合物、脂肪酸、鞘氨醇碱基和糖苷 联系。糖脂的灵敏定量分析将是 使用免疫化学、高效液相色谱和高效液相色谱-质谱仪开发 光谱技术。这些基因的发育性表达 将对中枢神经系统不同区域的糖脂进行研究。 在不同物种和神经突变体中的表达将是 调查过了。SGGL的细胞和亚细胞定位 在胚胎发育期间，大鼠的神经系统将被 通过化学和免疫化学方法进行研究。生物合成 将通过将各种不同的 糖基转移酶。SGGL基因表达的调控 将通过确定 各种糖基转移酶和水解酶。这些基础研究 将为今后关于职能作用的工作奠定基础 糖脂和糖蛋白上的SGG表位。