GLYCOCONJUGATES IN OLFACTORY CELL-CELL INTERACTIONS

嗅觉细胞间相互作用中的糖缀合物

• 批准号: 3217713
• 负责人: GERALD A SCHWARTING
• 金额: $ 20.69万
• 依托单位: EUNICE KENNEDY SHRIVER CTR MTL RETARDATN
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3217713
• 关键词: affinity chromatography; axon; carbohydrate structure; cell cell interaction; developmental neurobiology; electron microscopy; enzyme activity; enzyme linked immunosorbent assay; gas chromatography mass spectrometry; gene expression; glycolipids; glycoproteins; glycosyltransferase; hybridomas; immunocytochemistry; laboratory mouse; laboratory rat; lectin; light microscopy; monoclonal antibody; nervous system regeneration; neuronal guidance; neurons; olfactions; olfactory lobe; respiratory epithelium; sensory receptors; sialyltransferases; surface antigens; synaptogenesis

The objectives of this proposal are to understand the role of a specific group of cell surface glycolipids and glycoproteins in cell-cell interactions in olfactory receptor cells. It is designed to test the hypothesis that cell surface carbohydrate antigens interact with ligands on adjacent cell surfaces or on extracellular structures resulting in functionally relevant cellular interactions in the developing, mature and regenerating olfactory system. Three glycoconjugates were recently described which are specifically expressed on subsets of olfactory sensory neurons and their axons. Because of their unique distribution, all three glycoconjugates are candidate cell-cell interaction molecules which may participate in the establishment and maintenance of a functional olfactory system. Two of these molecules in particular may participate in mechanisms which guide olfactory axons to their targets in the olfactory bulb. A third glycoconjugate is expressed on olfactory neurons during an intermediate stage of their maturation and is likely to be relevant for studies of new olfactory connections in adult animals. In the proposed studies, the carbohydrate structures will be chemically characterized using chromatographic and mass spectrometric techniques. Carbohydrate binding proteins which are believed to participate in these cellular interaction will also be identified and chemically characterized. The detailed localization of these glycoconjugates and binding proteins will be analyzed during embryonic and postnatal development using immunocytochemical and electron microscopic techniques. In addition regeneration studies will be conducted to analyze the expression of the glycoconjugates during maturation of olfactory neurons. Glycosyltransferase studies will also be performed in order to understand the regional and age-related differences in expression of maturation-dependent glycoconjugates. This proposal represents a multifaceted approach, combining chemical, cellular, and anatomical analyses to define the role of a group of unique molecules to the olfactory system. These studies will provide insight into the molecular and cellular basis of olfactory structure and function and may illuminate mechanisms of pathogenesis in degenerative sensory disorders.

该提案的目标是了解特定的角色 细胞间的细胞表面糖脂和糖蛋白组 嗅觉受体细胞中的相互作用。它旨在测试 细胞表面碳水化合物抗原与配体相互作用的假设 在相邻的细胞表面或细胞外结构上导致 发育中、成熟阶段功能相关的细胞相互作用 和再生嗅觉系统。 最近描述了三种糖复合物，它们具体是 在嗅觉感觉神经元及其轴突的子集上表达。 由于其独特的分布，所有三种复合糖都 可能参与细胞间相互作用的候选分子 建立和维护功能性嗅觉系统。两个 这些分子尤其可能参与指导的机制 嗅觉轴突连接到嗅球中的目标。第三个 糖缀合物在中间过程中在嗅觉神经元上表达 它们的成熟阶段，可能与以下研究相关 成年动物的新嗅觉联系。 在拟议的研究中，碳水化合物结构将通过化学方法 使用色谱和质谱技术进行表征。 据信参与这些的碳水化合物结合蛋白 细胞相互作用也将被识别并通过化学方法 特点。这些糖复合物的详细定位和 结合蛋白将在胚胎和出生后进行分析 使用免疫细胞化学和电子显微镜进行开发 技术。此外，还将进行再生研究 分析糖复合物在成熟过程中的表达 嗅觉神经元。糖基转移酶研究也将在 为了了解地区和年龄相关的差异 成熟依赖性糖复合物的表达。这个提议 代表了一种多方面的方法，结合了化学、细胞和 解剖分析来定义一组独特分子的作用 嗅觉系统。 这些研究将提供对分子和细胞基础的深入了解 嗅觉结构和功能的研究，并可能阐明嗅觉机制 退行性感觉障碍的发病机制。