REGULATION OF PHARYNGEAL PUMPING IN PARASITIC NEMATODES

寄生线虫咽泵的调节

• 批准号: 7339642
• 负责人: Richard Walter Komuniecki
• 金额: $ 26.79万
• 依托单位: UNIVERSITY OF TOLEDO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7339642
• 关键词: Abbreviations; Adult; Agonist; Ascaris suum; Behavior; Binding; Binding Proteins; Biogenic Amine Receptors; Biogenic Amines; Biological Models; Caenorhabditis elegans; Complex; Coupling; Dominant-Negative Mutation; Dopamine; G Protein-Coupled Receptor Genes; G-Protein-Coupled Receptors; Goals; Grant; Homologous Gene; Individual; Ivermectin; Life; Ligands; Link; Liquid substance; Localized; Locomotion; Muscle Contraction; Nematoda; Neurons; Numbers; Octopamine; PDZ protein; PTEN gene; Parasitic nematode; Pharmacology; Pharyngeal structure; Phosphoric Monoester Hydrolases; Play; Preparation; Process; Protein Binding Domain; Protein Overexpression; Proteins; Pump; Regulation; Research Personnel; Role; Scaffolding Protein; Screening procedure; Sequence Alignment; Serotonin; Signal Pathway; Signal Transduction; Signaling Protein; Specificity; Testing; Tissues; Tyramine; Vertebrates; Yeasts; base; design; drug discovery; egg; feeding; glutamate-gated chloride channel; in vivo; mutant; novel; presynaptic; programs; receptor; receptor function; research study; serotonin receptor; tyramine receptor

DESCRIPTION (provided by the applicant): Biogenic amines, such as serotonin, tyramine, octopamine and dopamine regulate a number of key processes in parasitic nematodes, including, feeding, pharyngeal pumping, locomotion, egg-laying and many more complex behaviors. During the previous grant period, we have begun to characterize the pharmacology, coupling and localization of a number of biogenic amine receptors in both free-living and parasitic nematodes with the goal of identifying the specific receptors regulating these key processes. During the course of these studies, we have also identified a novel tyraminergeric signaling pathway and presynaptic 5-HT receptor-linked signaling complexes that are localized by a multi-PDZ domain containing scaffolding protein that appear to be essential for efficient signal transduction. The present study is focused on the definitive identification of the biogenic amine receptors regulating pharyngeal pumping in the parasitic nematode, Ascaris suum, on the assumption that interference with these receptors, especially by stimulating inhibitory inputs, as has been described for ivermectin and glutamate-gated chloride channels, will have a deleterious effect of the worms. In addition, we hypothesize that receptor localization can be as important as receptor function for effective signal transduction and plan to test this hypothesis using mutants and a "dominant negative" approach, once the other components of these multi-protein signaling complexes have been confirmed by direct protein interaction and in vivo co-localization.

描述（由申请人提供）：生物胺，例如血清素、酪胺、章鱼胺和多巴胺调节寄生线虫的许多关键过程，包括摄食、咽部泵送、运动、产卵和许多更复杂的行为。在上一个资助期间，我们已经开始表征自由生活和寄生线虫中许多生物胺受体的药理学、偶联和定位，目的是确定调节这些关键过程的特定受体。 在这些研究过程中，我们还发现了一种新的酪胺能信号通路和突触前 5-HT 受体相关信号复合物，它们由含有支架蛋白的多 PDZ 结构域定位，这似乎对于有效的信号转导至关重要。本研究的重点是明确鉴定调节寄生线虫猪蛔虫咽部泵送的生物胺受体，假设干扰这些受体，特别是通过刺激抑制性输入，如伊维菌素和谷氨酸门控氯通道所描述的那样，将对蠕虫产生有害影响。此外，我们假设受体定位与有效信号转导的受体功能一样重要，并计划在这些多蛋白信号复合物的其他成分通过直接蛋白质相互作用和体内共定位得到证实后，使用突变体和“显性阴性”方法来检验这一假设。