权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Functional study of the Ras-MAP kinase pathway in the nervous system

神经系统 Ras-MAP 激酶通路的功能研究

基本信息

批准号：
13480224
负责人：
IINO Yuichi
金额：
$ 10.82万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

The Ras-MAP kinase (MAPK) signaling pathway is known to transmit extracellular signals into the cells and to regulate cell proliferation and differentiation. On the other hand, evidences are emerging for other roles for the pathway in the nervous system, especially in neuronal plasticity. However, its exact functions are not fully understood. This study utilized Caenorhabditis elegans, which has advantages in genetics, anatomy, and ethology, to clarify the functions of the Ras-MAPK pathway in the nervous system.We have previously found that the C. elegans MAPK is activated in the olfactory neurons by odorant stimulus and its functions in the olfactory neurons is necessary for efficient olfaction. The present study pushed forward these findings and revealed that the Ras-MAPK pathway also plays important roles in odor adaptation. We first established a new assay system for odor adaptation and named it early adaptation. In the early adaptation assay, worms exposed to the odorant for five minutes showed dramatically reduced response to the odorant (chemotaxis). Several mutants of the Ras-MAPK pathway showed severe defects in early adaptation. Interestingly, this adaptation is not caused by down-regulation occurring in the olfactory neurons, but was dependent on the neural network. Namely, AIY interneurons, that receive inputs from olfactory neurons, were essential for this form of adaptation. MAPK is activated by odorant stimulus not only in the olfactory neurons but also in AIY interneurons. Cell specific expression of the ras gene revealed that Ras is required in AIY for adaptation. These results suggest that the Ras-MAPK pathway acts in olfactory neurons for odor perception, while its functions in the AIY interneurons are required for odor adaptation.

Ras-MAPK信号通路是已知的将细胞外信号传递到细胞内，调节细胞增殖和分化的信号通路。另一方面，该通路在神经系统，特别是在神经元可塑性中的其他作用的证据也在不断涌现。然而，它的确切功能还没有完全被理解。本研究利用在遗传学、解剖学和行为学方面具有优势的秀丽线虫，阐明Ras-MAPK通路在神经系统中的功能。我们先前发现，线虫MAPK在嗅神经元中被气味刺激激活，其在嗅神经元中的功能是有效嗅觉所必需的。本研究推进了这些发现，并揭示了Ras-MAPK通路在气味适应中也发挥着重要作用。我们首先建立了一种新的气味适应测试系统，并将其命名为早期适应。在早期适应试验中，蠕虫暴露在气味中五分钟后，对气味的反应(趋化性)显著降低。Ras-MAPK途径的几个突变体在早期适应中显示出严重的缺陷。有趣的是，这种适应并不是由嗅觉神经元的下调引起的，而是依赖于神经网络。也就是说，接受嗅觉神经元输入的AIY中间神经元对这种形式的适应是必不可少的。气味刺激不仅在嗅觉神经元激活MAPK，而且在AIY中间神经元也激活MAPK。Ras基因的细胞特异性表达表明，RAS在AIY中是适应所需的。这些结果表明，Ras-MAPK通路在嗅觉神经元中起作用，而它在AIY中间神经元中的作用是气味适应所必需的。