NEUROTRANSMITTER FUNCTION IN C. ELEGANS

线虫的神经递质功能

• 批准号: 6196706
• 负责人: ERIK M JORGENSEN
• 金额: $ 33万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6196706
• 关键词: Caenorhabditis elegans; GABA receptor; glutamate transporter; neurotransmitters; protein structure function

Neurotransmitters are released into the synaptic cleft using a common set of proteins involved in synaptic vesicle exocytosis and endocytosis. By contrast, certain synaptic proteins must be tailored to the needs of each specific neurotransmitter. These neurotransmitter-specific functions include biosynthetic enzymes, transporters for translocation across vesicular and plasma membranes, and specialized receptors on the postsynaptic surface. My laboratory is engaged in a longterm project to identify the gene products required by specific neurotransmitters. We are taking a genetic approach in the nematode Caenorhabditis elegans to identify mutants defective for the functions of a specific neurotransmitter, we then clone the cognate genes and characterize the proteins using biochemical assays. We propose to identify and characterize three proteins which function in neurotransmission: (1) the vesicular glutamate transporter, which as yet, remains uncharacterized, (2) a potential ancillary protein to the vesicular GABA transporter encoded by the unc-46 gene, (3) a novel excitatory GABA receptor encoded by the exp-1 gene. These studies are likely to result directly in the identification of vertebrate homologs of these proteins. Eventually, these experiments will lead to a better understanding of how the molecular structures of these proteins confer their functional properties. Ultimately, these studies might help explain the molecular behavior of neuroactive drugs and lead to the development of new and more specific pharmaceuticals which act on individual neurotransmitter systems.

神经递质使用一组参与突触囊泡胞吐和内吞作用的常见蛋白质释放到突触裂口中。 相比之下，某些突触蛋白必须根据每个特定神经递质的需求量身定制。 这些神经递质特异性功能包括生物合成酶，用于跨囊泡和质膜的转运蛋白，以及突触后表面上的专门受体。我的实验室正在进行一个长期项目，以识别特定神经递质所需的基因产品。 我们正在秀丽隐杆线虫中采用一种遗传方法，以鉴定出特定神经递质功能有缺陷的突变体，然后我们克隆同源基因并使用生化测定法对蛋白质进行表征。我们建议识别和表征三种在神经传递中起作用的蛋白质：（1）囊泡谷氨酸转运蛋白，迄今为止尚未进行尚未进行，（2）（2）潜在的辅助蛋白与囊泡GABA转运蛋白的潜在辅助蛋白，由UNC-46基因编码，（3）新型的兴奋性gaba受体受体代码。这些研究可能直接导致这些蛋白质的脊椎动物同源物的鉴定。最终，这些实验将更好地理解这些蛋白质的分子结构如何赋予其功能特性。最终，这些研究可能有助于解释神经活性药物的分子行为，并导致对单个神经递质系统作用的新型和更具体的药物的发展。