SULFOGLUCURONYL (HNK-1) CARBOHYDRATE IN NEUROGENESIS

神经发生中的磺基葡萄糖醛酸 (HNK-1) 碳水化合物

• 批准号: 6564623
• 负责人: FIROZE B JUNGALWALA
• 金额: $ 10.66万
• 依托单位: EUNICE KENNEDY SHRIVER CTR MTL RETARDATN
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6564623
• 关键词: aminosugar; carbohydrate metabolism; cell adhesion molecules; cell cell interaction; cell migration; cerebral cortex; chemical structure function; developmental neurobiology; embryo /fetus cell /tissue; gene expression; glucuronates; glucuronosyltransferase; glycolipids; glycoproteins; immunocytochemistry; in situ hybridization; laboratory mouse; laboratory rat; lectin; lipid biosynthesis; molecular cloning; neurogenesis; neurogenetics; neuronal guidance; sulfation; surface antigens

The long term goal of this study is to test the hypothesis that interaction of sulfoglucuronyl carbohydrate (SGC) and its binding protein (SBP) involve SBP-1 on neurons and its ligand SGC on processes on neurons and glia, thus providing a guidance (SGC) and its binding protein (SBP) involve SBP-1 on neurons and its ligand SGC on processes of neurons and glia, thus providing a guidance and signaling mechanism for cell migration and process outgrowth. A large number of experiments toward that goal are planned in the four aims. Specific Aim 1 is to study neurite outgrowth and neuronal migration in explant cultures of embryonic cerebral cortex and thick slice tissue culture systems. Various antibodies and glycolipids will be added to determine the effect on migration and neuritogenesis. Specific Aim 2 is to clone the GlcNAc-Tr that has been described as the key regulatory enzyme for synthesis of Lc0se3Cer, the SGGC precursor. The main approach will be expression cloning, with the alternative use of a suppression subtractive hybridization cDNA library they recently constructed. Specific Aim 3 is to investigate the role of GT gene expression in regulation of SGC synthesis on glycolipids and glycoproteins during development . One hypothesis is that GlcNAc-Tr will be involved in expression of sulfoglucuronyl glycolipid (SGGL) rather than glycoproteins bearing the SGC epitope, which would presumably utilize other GlcNAc transferases.

本研究的长期目标是验证以下假设：磺基葡萄糖醛酸基碳水化合物（SGC）及其结合蛋白（SBP）的相互作用涉及SBP-1在神经元上的作用及其配体SGC在神经元和胶质细胞上的作用，从而提供指导（SGC）及其结合蛋白（SBP）涉及SBP-1在神经元上的作用及其配体SGC在神经元和胶质细胞上的作用，从而为细胞迁移和过程生长提供指导和信号机制。这四个目标计划为实现这一目标进行大量实验。具体目标1是研究胚胎大脑皮层组织块培养和厚片组织培养系统中神经突起的生长和神经元的迁移。将加入各种抗体和糖脂，以确定对迁移和轴突发生的影响。具体目标2是克隆GlcNAc-Tr，其已被描述为合成SGGC前体Lc 0 se 3Cer的关键调节酶。主要的方法将是表达克隆，与他们最近构建的抑制性消减杂交cDNA文库的替代使用。具体目标3是研究GT基因表达在发育过程中对糖脂和糖蛋白的SGC合成的调节作用。一种假设是GlcNAc-Tr将参与磺基葡糖醛酸基糖脂（SGGL）而不是携带SGC表位的糖蛋白的表达，其可能利用其他GlcNAc转移酶。