GLYCOCONJUGATES IN OLFACTORY CELL-CELL INTERACTIONS

本提案的目的是了解特定的 细胞间的一组细胞表面糖脂和糖蛋白 嗅觉受体细胞的相互作用。它旨在测试 细胞表面糖抗原与配体相互作用假说 在邻近的细胞表面或细胞外结构上，导致 在发育、成熟和成熟的过程中， 和再生嗅觉系统。 最近描述了三种糖缀合物，其特异性地 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，所有三种糖缀合物都是 候选细胞-细胞相互作用分子，其可能参与细胞间相互作用。 建立和维持功能性嗅觉系统。两 这些分子尤其可能参与引导 嗅觉轴突到达它们的目标嗅球。第三 糖缀合物在嗅觉神经元上表达， 这是他们成熟的阶段，可能与研究有关， 成年动物的新嗅觉连接 在拟议的研究中，碳水化合物结构将以化学方式 使用色谱和质谱技术表征。 碳水化合物结合蛋白被认为参与这些 细胞间的相互作用也将被识别， 表征了这些糖缀合物的详细定位和 结合蛋白将在胚胎和出生后进行分析 利用免疫细胞化学和电子显微镜 技术.此外，还将进行再生研究， 分析糖缀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 为了了解区域和年龄相关的差异， 成熟依赖性糖缀合物的表达。这项建议 代表了一种多方面的方法，结合了化学，细胞， 解剖分析，以确定一组独特的分子的作用， 嗅觉系统 这些研究将提供深入了解分子和细胞基础 嗅觉的结构和功能，并可能阐明机制， 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.