The Function of Arrestin in Drosophila Behavior

Arrestin 在果蝇行为中的作用

• 批准号: 6544272
• 负责人: Gregg W Roman
• 金额: $ 28.6万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 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 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6544272
• 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）：动物从环境中接收的大部分信息是通过G蛋白偶联受体（GPCR）收集的。减弱这些受体的信号传导的能力将是最期望的，以便具有对环境的准确感知。此外，突触可塑性和学习所需的感觉输入之间的关联也应该取决于通过这些受体的信号传导的精确时间和幅度。抑制蛋白的一个主要功能是下调激活的GPCR，这表明这些蛋白质对感觉处理和关联过程至关重要。本研究的目的是了解kurtz非视觉抑制蛋白在果蝇神经系统中的功能，从而确定激动剂诱导的G蛋白偶联受体脱敏在行为中的重要性。拟议的研究将利用突变的库尔茨抑制蛋白和新产生的转基因，以检查库尔茨抑制蛋白在感觉加工的功能，并在负强化联想和操作性条件反射学习范式。具体来说，这些实验将提出一个问题，即激活的GPCR的快速脱敏和重新脱敏是否是准确的嗅觉处理以及学习和记忆过程的必要条件。其他实验将表征库尔茨抑制蛋白的生物化学和细胞特性。这些结果可以允许在行为表型和与特定GPCR的相互作用之间绘制特定的相关性。如果激动剂诱导的GPCR脱敏对于准确地确定神经元输入的时间以最大化信息关联确实至关重要，那么抑制蛋白可能成为认知增强剂的有吸引力的靶点，其最终可能有助于治疗与衰老相关的记忆衰退以及包括阿尔茨海默病在内的认知障碍。