Molecular Biological Analyses of the Neural Functions of the Nematode C. elegans

线虫神经功能的分子生物学分析 线虫

• 批准号: 09480190
• 负责人: KATSURA Isao
• 金额: $ 8.19万
• 依托单位: National Institute of Genetics
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09480190/
• 关键词: behavior; molecular biology; C. elegans; chemtaxis; associative learning; adaptation; mutants; sensory cilia; 線虫; C.elegans; 神経機能; 行動異常; T-box; WD40; 感覚受容; イオンチャネル; グルタミン酸受容体

We studied the genetic basis of behavior by molecular biological methods, using the nematode C. elegans. (a) The class 1 flr genes, which are related to resistance to fluoride ion, growth rates, defecation cycle periods and the processing of sensory signals, encode an ion channel, a protein kinase and a kinase-like molecule. In this study we showed that they constitute a regulatory system that acts in the intestine and that regulates many food-related functions. The flr-2 gene, which is located in the downstream of the regulatory system, encoded a secretary protein expressed in certain neurons. (b) The sdf-13 gene, which is identified by synthetic dauer-constitutive mutations, encoded a transcriptional factor homologous to the mammalian Tbx2 and was required for the adaptation of chemotaxis to certain odorants. (c) The gene for the ut236 mutation, which confers preference of copper ion over chemotaxis to odorants, encoded a secretory protein having an LDLa domain and was required for normal associative learning. The ut235 mutant had abnormality in the response in which starvation desensitizes the avoidance of copper ion. (d) The che-2 gene, which is required for the extension of sensory cilia, encoded a novel protein that has WD40 repeats and that is localized at cilia. Using the che-2 clone, we succeeded in restoring the che-2 function in a subset of sensory neurons or at any stage of development in che-2 mutants. This experiment revealed a dynamic nature of sensory cilia. All these studies demonstrated that behavior can be analyzed at molecular and cellular levels by molecular biological methods and that such studies lead to new discoveries.

本研究利用线虫C.优美的(a)1类flr基因编码离子通道、蛋白激酶和激酶样分子，与氟离子抗性、生长速率、排便周期和感觉信号处理有关。在这项研究中，我们表明，它们构成了一个调节系统，在肠道中发挥作用，并调节许多与食物相关的功能。flr-2基因位于调控系统的下游，编码一种在某些神经元中表达的分泌蛋白。(b)sdf-13基因，这是确定的合成dauer组成型突变，编码的转录因子同源的哺乳动物Tbx 2和所需的适应某些气味的趋化性。(c)ut 236突变的基因，赋予偏好的铜离子对气味的趋化性，编码一种分泌蛋白具有LDLa域和所需的正常联想学习。ut 235突变体对铜离子的回避反应出现异常，表现为饥饿使铜离子回避反应不敏感。(d)的che-2基因，这是所需的感觉纤毛的延伸，编码一种新的蛋白质，具有WD 40重复，并定位于纤毛。使用che-2克隆，我们成功地恢复了che-2突变体中感觉神经元亚群或任何发育阶段的che-2功能。这个实验揭示了感觉纤毛的动态性质。所有这些研究都表明，可以通过分子生物学方法在分子和细胞水平上分析行为，并且这些研究会导致新的发现。

项目成果

M. Take-uchi et al.: "An ion channel of the degenerin/epithelial sodium channel superfamily controls the defecation rhythm in Caenorhabditis elegans"Proc. Natl. Acad. Sci. USA. 95. 11775-11780 (1998)

M. Take-uchi 等人：“退化蛋白/上皮钠通道超家族的离子通道控制着秀丽隐杆线虫的排便节律”Proc.

A. R. Winnier et al.: "UNC-4/UNC-37-dependent repression of moter neuron-specific genes controls synaptic choice Caenorhabditis elegans"Genes & development. 13. 2774-2786 (1999)

A. R. Winnier 等人：“运动神经元特异性基因的 UNC-4/UNC-37 依赖性抑制控制秀丽隐杆线虫的突触选择”基因

A.R.Winnier, J.Y.-J.Meir, J.M.Ross, N.Tavernarakis, M.Driscoll, T.Ishihara, I.Katsura and D.M.Miller III: "UNC-4/UNC-37-dependent repression of moter neuron-specific genes controls synaptic choice in Caenorhabditis elegans."Genes & Development. 13. 2774-2

A.R.Winnier、J.Y.-J.Meir、J.M.Ross、N.Tavernarakis、M.Driscoll、T.Ishihara、I.Katsura 和 D.M.Miller III：“运动神经元特异性基因控制的 UNC-4/UNC-37 依赖性抑制

M. Fujiwara et al.: "A novel WD40 protein, CHE-2, acts cell-autonomously in the formation of C. elegans sensory cilia"Development. 126. 4839-4848 (1999)

M. Fujiwara 等人：“一种新型 WD40 蛋白 CHE-2，在秀丽隐杆线虫感觉纤毛的形成中以细胞自主方式发挥作用”开发。

Masaya Take-uchi: "An ion channel of the degenerin/epithelial sodium channel superfamily controls the defecation rhythm in C.elegans." Proceedings of the National Academy of Science of the USA. 95. 11775-11780 (1998)

Masaya Take-uchi：“退化蛋白/上皮钠通道超家族的离子通道控制着秀丽隐杆线虫的排便节律。”