GLYCOCONJUGATES IN OLFACTORY CELL-CELL INTERACTIONS

这项建议的目标是了解特定的 细胞-细胞内的一组细胞表面糖脂和糖蛋白 嗅觉感受器细胞间的相互作用。它的设计目的是测试 细胞表面糖类抗原与配体相互作用的假说 在相邻的细胞表面或细胞外结构上导致 发育、成熟过程中与功能相关的细胞相互作用 和再生嗅觉系统。 最近描述了三种糖偶联物，它们具体是 在嗅觉感觉神经元及其轴突的亚群上表达。 由于其独特的分布，所有三种糖偶联物都是 候选细胞-细胞相互作用分子可能参与 功能嗅觉系统的建立和维护。其中两个 尤其是这些分子可能参与引导 嗅觉轴突到达它们嗅球中的靶点。三分之一 糖偶联物在嗅觉神经元上表达 它们处于成熟阶段，这可能与对它们的研究有关 成年动物的新嗅觉联系。 在拟议的研究中，碳水化合物的结构将是化学的。 用层析和质谱学技术进行了表征。 碳水化合物结合蛋白被认为参与了这些 细胞的相互作用也将被识别和化学 特色化的。这些糖结合物的详细定位和 结合蛋白将在胚胎和出生后进行分析 免疫细胞化学和电子显微镜技术的研究进展 技巧。此外，还将进行再生研究，以 分析糖偶联物在成熟过程中的表达 嗅觉神经元。糖基转移酶的研究也将在 为了了解地区和年龄方面的差异， 成熟度依赖的糖偶联物的表达。这项建议 代表了一种多方面的方法，结合了化学、细胞和 解剖学分析以确定一组独特的分子在 嗅觉系统。 这些研究将提供对分子和细胞基础的洞察。 嗅觉的结构和功能，并可能阐明 退行性感觉障碍的发病机制。

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.