C. elegans olfactory adaptation

C. 线虫嗅觉适应

• 批准号: 7294454
• 负责人: Noelle D L 'Etoile
• 金额: $ 1.37万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-05 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7294454
• 关键词: Caenorhabditis elegans; biological signal transduction; cGMP dependent protein kinase; cell nucleus; endocytosis; gene expression; genetic transcription; green fluorescent proteins; helminth genetics; intracellular transport; mutant; neural plasticity; olfactory nerve; olfactory stimulus; protein localization; protein transport

DESCRIPTION (provided by applicant): To respond appropriately to its dynamic environment, a sensory neuron must attenuate its response to persistent stimuli while remaining sensitive to a novel stimulus. This is accomplished by specifically turning down or adapting, the response of the receptor. Accurate adaptation of signaling events is crucial throughout the nervous system; failure to down-regulate the G-protein coupled receptor (GPCR) rhodopsin signaling leads to retinal degeneration and blindness in Oguchi disease (Chen et al., 1999) while hyperadaptation of the mu opioid GPCR signaling by morphine leads to tolerance associated with opiate addiction (Whistler et al., 1998). Though the initial signal transduction events and rapid turn off of such GPCR-mediated signaling are well described, little is known about how these neurons adapt to prolonged stimulation. In this grant, we propose to identify the molecules and molecular processes responsible for long lasting adaptation of GPCR signaling in C. elegans. Study of a model organism that is tractable to both genetics and cell biology affords us the opportunity to examine the molecular processes that deactivate odor signaling. We will use cell biological techniques to examine the initiation of long-term adaptation by the PKG, EGL-4. In so doing, we will characterize the role that such basic biological processes as transcription, and endocytosis play in promoting adaptation. Finally, we will identify new molecules required to initiate adaptation of a GPCR signaling. Biophysical, biochemical, and protein trafficking changes that regulate adaptation in C. elegans sensory neurons are likely to have their counterparts in the mammalian central nervous system. The genes identified as being important for initiating long-term adaptation are likely to have conserved functions in diverse cell types that rely on adaptation-like processes to respond to prolonged or repeated signaling.

描述(由申请人提供)： 为了对其动态环境做出适当的反应，感觉神经元必须减弱其对持续刺激的反应，同时对新的刺激保持敏感。这是通过特别地拒绝或调整受体的反应来实现的。信号事件的准确适应在整个神经系统中都是至关重要的；未能下调G蛋白偶联受体(GPCR)视紫红质信号会导致Oguchi病的视网膜退化和失明(Chen等人，1999年)，而吗啡对u阿片类GPCR信号的过度适应会导致与阿片成瘾相关的耐受(Wvisler等人，1998年)。虽然最初的信号转导事件和这种GPCR介导的信号迅速关闭已经被很好地描述，但关于这些神经元如何适应长时间的刺激知之甚少。在这项资助中，我们建议确定在线虫中负责GPCR信号长期适应的分子和分子过程。 对一种同时适用于遗传学和细胞生物学的模式生物的研究，为我们提供了研究去激活气味信号的分子过程的机会。我们将使用细胞生物学技术来检测PKG，EGL-4启动长期适应的情况。在这样做的过程中，我们将描述转录和内吞等基本生物过程在促进适应方面所起的作用。最后，我们将确定启动GPCR信号适应所需的新分子。调节线虫感觉神经元适应的生物物理、生化和蛋白质运输变化可能在哺乳动物的中枢神经系统中也有对应的变化。被认为对启动长期适应很重要的基因可能在不同类型的细胞中具有保守的功能，这些细胞类型依赖于类似适应的过程来对长时间或重复的信号做出反应。