Analyses of Localization and Function of C. elegans Synaptic Proteins

线虫突触蛋白的定位和功能分析

• 批准号: 13680864
• 负责人: KUROYANAGI Hidehito
• 金额: $ 2.18万
• 依托单位: Tokyo Medical & Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680864/
• 关键词: Genes; Anatomy; Genome; Neuroscience; Neuron; Synapse; C. eleeans

In order to obtain genetic tools to study further the formation of pre- and postsynaptic structures during development as well as the mechanisms of targeting postsynaptic proteins to synapses, we searched C. elegans genome for genes homologous to postsynaptic proteins recently identified in mammalian postsynaptic structures. We confirmed their expression by amplifying cDNA fragments. Sequencing of these cDNA fragments revealed genomic organization and amino acid sequence of the protein. Some of these proteins possess highly conserved amino acid sequences and overall domain organization, A C. elegans homologue (C25F6.2) of Drosophila Discs Large and mammalian PSD-95/SAP90 family proteins consists of three PDZ domains, one SH3 domain and a guanylate kinase domain. A homologue (formerly A assigned as K01A6.2 and K01A6.1) of S-SCAM/ARIP/MAGI family proteins associating with various kinds of receptor proteins consists of one guanylate kinase domain, two tandem WW domains and five PDZ domains. A homologue (C33B4.3) of synamon/shank, proteins coupling NMDAR/PSD-95 complex and mGluR/Homer complex, possesses ankyrin repeats, a PDZ domain and a SAM domain. Characterization of these C. elegans genes suggests importance of molecular structures that may be involved the postsynaptic specialization.

为了获得进一步研究发育过程中突触前和突触后结构的形成以及突触后蛋白靶向突触的机制的遗传工具，我们检索了C.与最近在哺乳动物突触后结构中鉴定的突触后蛋白同源的基因。我们通过扩增cDNA片段证实了它们的表达。这些cDNA片段的测序揭示了基因组组织和蛋白质的氨基酸序列。这些蛋白质中的一些具有高度保守的氨基酸序列和整体结构域组织，A C。果蝇盘状大蛋白和哺乳动物PSD-95/SAP 90家族蛋白的Elegans同源物（C25F6.2）由三个PDZ结构域、一个SH 3结构域和一个鸟苷酸激酶结构域组成。S-SCAM/ARIP/MAGI家族蛋白的一个同源物（以前称为K01A6.2和K01A6.1）与各种受体蛋白相关，由一个鸟苷酸激酶结构域、两个串联的WW结构域和五个PDZ结构域组成。C33B4.3是一种偶联NMDAR/PSD-95复合物和mGluR/Homer复合物的蛋白质，具有锚蛋白重复序列、PDZ结构域和SAM结构域。这些C. elegans基因提示可能参与突触后特化的分子结构的重要性。

项目成果

Ikegaya Y, et al.: "Aberrant synaptic transmission in the hippocampal CA3 region and cognitive deterioration in protein-repair enzyme-deficient mice"Hippocampus. 11. 287-298 (2001)

Ikegaya Y 等人：“海马 CA3 区的异常突触传递和蛋白质修复酶缺陷小鼠的认知恶化”海马。

Nakai D, et al.: "Mouse homologue of, coq7/clk-1, longevity gene in Caenorhabditis elegans, is essential for coenzyme Q synthesis, maintenance of mitochondrial integrity, and neurogenesis"Biochem Biophys Res Commun. 289. 463-471 (2001)

Nakai D 等人：“秀丽隐杆线虫长寿基因 coq7/clk-1 的小鼠同源物对于辅酶 Q 合成、维持线粒体完整性和神经发生至关重要”Biochem Biophys Res Commun。

Okabe S, et al.: "Rapid redistribution of the postsynaptic density protein PSD-Zip45 (Homer 1c) and its differential regulation by NMDA receptors and calcium channels"J Neuroscience. 21. 9561-9571 (2001)

Okabe S 等人：“突触后密度蛋白 PSD-Zip45 (Homer 1c) 的快速重新分布及其受 NMDA 受体和钙通道的差异调节”J Neuroscience。

Takahashi M, et al.: "Mouse coq7/clk-1 orthologue rescued slowed rhythmic behavior and extended life span of clk-1 longevity mutant in Caenorhabditis elegans"Biochem Biophys Res Commun. 286. 534-540 (2001)

Takahashi M 等人：“小鼠 coq7/clk-1 直系同源物挽救了秀丽隐杆线虫中 clk-1 长寿突变体减慢的节律行为并延长了寿命”Biochem Biophys Res Commun。

Okabe S, et al.: "Spine formation and correlated assembly of presynaptic and postsynaptic molecules"J Neuroscience. 21. 6105-6114 (2001)

Okabe S 等人：“脊柱形成和突触前和突触后分子的相关组装”J Neuroscience。