Elucidation of The Molecular Mechanims of Chemotaxis and Its Plasticity in the Nematode Caenorhabditis elegans

秀丽隐杆线虫趋化性及其可塑性分子机制的阐明

• 批准号: 11680672
• 负责人: IINO Yuichi
• 金额: $ 2.43万
• 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 (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680672/
• 关键词: Nematode; Caenorhabditis elegans; Chemotaxis; Olfaction; Associative learning; Ras; Mitogen-activated protein kinase; Odorant; 環状ヌクレオチド依存性チャネル; 可塑性; 嗅覚抑圧

The Ras-MAPK (mitogen-activated protein kinase) signal transduction pathway is well known to play a major role in the regulation of cellular proliferation and differentiation. In the model organism Caenorhabditis elegans, the Ras-MAPK pathway plays key roles in vulval induction, progression of meiosis, and several other developmental events1. However, although LET-60 Ras is expressed in many neurons2, its function in the nervous system is not known in this organism. Here we report that the Ras-MAPK pathway plays an essential role in olfactory neurons in C.elegans. Mutational inactivation and hyperactivation of this nathway impairs the chemotactic response of the animals to a set of odorants. The expression of wild type and a mutant form of let-60 ras by a heat shock promoter and a cell-specific promoter indicates that the normal activity of LET-60 is required in mature olfactory neurons. Application of the odorant isoamylalcohol to wild type animals leads to the activation of MAP kinas … More e in olfactory neurons within 10 seconds. This induction is dependent on the function of the nucleotide-gated channel TAX-2/TAX-4 and the voltage-activated calcium channel subunit UNC-2. These results suggest a dynamic role for the pathway in perception and transmission of sensory signals in olfactory neurons.While the basic functions of the nervous system of Caenorhabditis elegans have been extensively studied, its behavioral plasticities are not fully explored due to the limited availability of assay systems. We report here a simple form of chemotaxis plasticity in this organism. When worms are starved on plates including NaCl, their chemotaxis to NaCl drops dramatically. This conditioning requires both the presence of NaCl and the absence of bacteria, indicating that it is not a mere adaptation or habituation, but is likely to be a form of associative learning. While chemotaxis to volatile chemoattractants does not change significantly after conditioning with NaCl, chemotaxis to other water-soluble attractants also decreased. This suggests that an altered response of a cell (s) specifically involved in chemotaxis to water-soluble chemoattractants is responsible for the behavioral alteration. The decrease in chemotaxis occurred slowly over 3-4 hours of conditioning and returned quickly to the original level when either of the conditioning stimuli, NaCl or starvation, was removed. The application of serotonin partially blocked this drop in chemotaxis, consistent with the proposed function of this neurotransmitter in food signaling. We have isolated three mutants with reduced plasticity as assayed in this paradigm. This assay system expands the opportunities in which molecular and cellular mechanisms of behavioral plasticity can be studied in C.elegans. Less

丝裂原活化蛋白激酶（mitogen-activated protein kinase，Ras-MAPK）信号转导通路在细胞增殖和分化的调控中起重要作用。在模式生物秀丽隐杆线虫中，Ras-MAPK通路在外阴诱导、减数分裂进展和其他几个发育事件中起关键作用1。然而，尽管LET-60 Ras在许多神经元中表达2，但其在神经系统中的功能在该生物体中尚不清楚。在这里，我们报告说，Ras-MAPK通路起着至关重要的作用，在秀丽隐杆线虫的嗅觉神经元。这种神经通路的突变失活和过度激活会损害动物对一组气味的趋化反应。野生型和突变形式的let-60 ras的热休克启动子和细胞特异性启动子的表达表明，LET-60的正常活性是需要在成熟的嗅觉神经元。将气味剂异戊醇应用于野生型动物导致MAP激酶的激活 ...更多信息 在10秒内嗅觉神经元中。这种诱导依赖于核苷酸门控通道TAX-2/TAX-4和电压激活的钙通道亚基TAX-2的功能。这些结果表明，在嗅觉neurons.While的神经系统的秀丽隐杆线虫的基本功能的感知和传递的感觉信号的途径的动态作用已被广泛研究，其行为可塑性没有充分探讨由于有限的可用性的测定系统。我们在这里报告一个简单的形式，在这种生物体的趋化可塑性。当蠕虫在含有NaCl的平板上饥饿时，它们对NaCl的趋化性急剧下降。这种条件作用需要NaCl的存在和细菌的缺乏，这表明它不仅仅是一种适应或习惯，而可能是一种联想学习的形式。而挥发性化学引诱剂的趋化性没有显着改变后，与NaCl调节，其他水溶性引诱剂的趋化性也下降。这表明，一个或多个细胞的改变的反应，特别是参与趋化性的水溶性化学引诱剂是负责的行为改变。趋化性的下降发生缓慢超过3-4小时的条件反射，并迅速恢复到原来的水平时，条件反射刺激，NaCl或饥饿，被删除。血清素的应用部分阻断了趋化性的下降，这与这种神经递质在食物信号传导中的功能一致。我们已经分离出三个突变体与减少可塑性在这个范例中进行了测定。该检测系统扩大了在秀丽隐杆线虫中研究行为可塑性的分子和细胞机制的机会。少

项目成果

Ohmachi,M.Sugimoto,A.Iino,Y.Yamamoto,M.: "kel-1,a novel kelch-related gene in Caenorhabditis elegans,is expressed in pharyngeal gland cells and is required for feeding process"Genens to Cells. 4. 325-327 (1999)

Ohmachi,M.Sugimoto,A.Iino,Y.Yamamoto,M.：“kel-1，一种新的秀丽隐杆线虫 kelch 相关基因，在咽腺细胞中表达，是进食过程所必需的”Genens to Cells。

T.Okuda,T.Haga,Y.Kanai,H.Endou,T.Ishihara and I.Katsura: "Identification and characterization on of the high-affinity choline transporter"Nature Neuroscience. 3. 120-125 (2000)

T.Okuda、T.Haga、Y.Kanai、H.Endou、T.Ishihara 和 I.Katsura：“高亲和力胆碱转运蛋白的鉴定和表征”《自然神经科学》。

Kunitomo,H. et al.: "A zinc-finger protein, Rst2p, regulates transcription of the fission yeast ste 11 (+) gene, which encodes a pivotal transcription factor for sexual development"Mol.Biol.Cell. 11. 3205-17 (2000)

国友，H.

Kawasaki, M., Hisamoto, N., Iino, Y., Yamamoto, M., Ninomiya-Tsuji, J.and Matsumoto, K.: "A Caenorhabditis elegans JNK signal transduction pathway regulates coordinated movement via type-D GABAergic motor neurons"EMBO J.. 18. 3604-15 (1999)

Kawasaki, M.、Hisamoto, N.、Iino, Y.、Yamamoto, M.、Ninomiya-Tsuji, J. 和 Matsumoto, K.：“秀丽隐杆线虫 JNK 信号转导途径通过 D 型 GABA 能运动神经元调节协调运动

Hirotsu, T., Saeki, S., Yamamoto, M.and Iino, Y.: "The Ras-MAPK pathway is important for olfaction in Caenorhabditis elegans"Nature. 404. 289-93 (2000)

Hirotsu, T.、Saeki, S.、Yamamoto, M. 和 Iino, Y.：“Ras-MAPK 通路对于秀丽隐杆线虫的嗅觉很重要”《自然》。