The Function of Arrestin in Drosophila Behavior

Arrestin 在果蝇行为中的作用

• 批准号: 7127025
• 负责人: Gregg W Roman
• 金额: $ 18.08万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127025
• 关键词: Drosophilidae; G protein; arrestins; behavior; biological signal transduction; ethology; gene mutation; learning; memory; nervous system; neurophysiology; olfactions; operant conditionings; receptor coupling; receptor expression; sensory mechanism; tissue /cell culture; transfection

DESCRIPTION (provided by applicant): Much of the information animals receive from the environment is gathered through G protein-coupled receptors (GPCRs). The ability to attenuate the signaling of these receptors would be most desirable in order to have an accurate perception of the environment. Additionally, the association between sensory inputs required for synaptic plasticity and learning should also be dependent on the precise timing and magnitude of signaling through these receptors. A primary function of arrestins, to down regulate activated GPCRs, suggests that these proteins are fundamental to the processes of sensory processing and association. The objective of the proposed research is to understand the function of the kurtz non-visual arrestin within the nervous system of Drosophila, and thereby determine the importance of agonist-induced desensitization of G protein-coupled receptors in behavior. The proposed studies will utilize mutants of the kurtz arrestin and newly generated transgenes to examine the function of the kurtz arrestin in sensory processing, and in both negatively-reinforced associative and operant conditioning learning paradigms. Specifically, the experiments will ask the question of whether the rapid desensitization and the resensitization of activated GPCRs is a requirement for accurate olfactory processing and in the processes of learning and memory. Additional experiments will characterize the biochemical and cellular properties of the kurtz arrestin. These results may allow for specific correlations to be drawn between behavioral phenotypes and the interactions with a specific GPCR. If agonist-induced desensitization of GPCRs is indeed critical to accurately time neuronal inputs so as to maximize informative associations, then arrestins may become attractive targets for cognitive enhancers that may eventually help treat aging associated memory decline as well as cognitive disorders including Alzheimer's disease.

描述（由申请人提供）：动物从环境中收到的许多信息都是通过G蛋白偶联受体（GPCR）收集的。为了准确地感知环境，最需要减弱这些受体的信号传导的能力。另外，突触可塑性所需的感觉输入与学习之间的感觉也应取决于通过这些受体的信号传导的精确时机和幅度。逮捕蛋白的主要功能，以降低调节活化的GPCR，这表明这些蛋白质是感觉处理和关联过程的基础。拟议的研究的目的是了解果蝇神经系统中库尔茨非视觉停滞的功能，从而确定激动剂诱导的行为中G蛋白偶联受体脱敏的重要性。拟议的研究将利用库尔茨阻滞蛋白和新产生的转基因的突变体来检查库尔茨阻止素在感觉处理中的功能，以及在负面增强的缔合性和操作方调节学习范式中的功能。具体而言，实验将询问一个问题，即激活的GPCR的快速脱敏和激活是对准确的嗅觉处理以及在学习和记忆过程中的要求。其他实验将表征库尔茨阻止素的生化和细胞特性。这些结果可以允许在行为表型与特定GPCR的相互作用之间提出特定的相关性。如果激动剂诱导的GPCR脱敏确实对于准确的时间神经元输入至关重要，以最大程度地提高信息性关联，那么逮捕蛋白可能会成为认知增强剂的有吸引力的靶标，这些目标可能最终有助于治疗相关的记忆力下降以及包括阿尔茨海默氏病在内的认知障碍。