C. elegans olfactory adaptation

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，同时保持对新刺激的敏感性。这是通过特异性地下调或适应受体的反应来实现的。信号传导事件的准确适应在整个神经系统中是至关重要的;未能下调G蛋白偶联受体（GPCR）视紫红质信号传导导致Oguchi病中的视网膜变性和失明（Chen等人，1999），而吗啡引起的μ阿片样物质GPCR信号传导的超适应导致与阿片成瘾相关的耐受性（Whistler等，1998年）。虽然最初的信号转导事件和这种GPCR介导的信号的快速关闭被很好地描述，但关于这些神经元如何适应长时间的刺激却知之甚少。在这项研究中，我们提出了确定的分子和分子过程，负责长期持久的适应GPCR信号在C。优雅 研究一种遗传学和细胞生物学都易于处理的模式生物，为我们提供了研究使气味信号失活的分子过程的机会。我们将使用细胞生物学技术来检查PKG，EGL-4的长期适应的启动。在此过程中，我们将描述转录和内吞作用等基本生物学过程在促进适应中的作用。最后，我们将确定启动GPCR信号适应所需的新分子。生物物理，生物化学和蛋白质运输的变化，调节适应C。线虫的感觉神经元可能在哺乳动物的中枢神经系统中有其对应物。被确定为启动长期适应的重要基因可能在依赖于适应样过程来响应延长或重复信号的不同细胞类型中具有保守的功能。

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.