Functional analysis of an RNA-binding protein, TLS, in neuronal dendrites.

神经元树突中 RNA 结合蛋白 TLS 的功能分析。

• 批准号: 15590285
• 负责人: TAKUMI Toru
• 金额: $ 2.3万
• 依托单位: Osaka Bioscience Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590285/
• 关键词: Synaptic plasticity; neuron, neuronal dendrite; dendritic shine. RNA-binding protein; actin. glutamete; アクチン; RNA結合蛋白; グルタミン酸; 高次脳機能; RNA結合タンパク; グルタミン酸シグナル; mRNA; 大脳新皮質; 神経樹状突起

Neuronal dendrites, together with dendritic spines, exhibit enormously diverse structure. Selective targeting and local translation of mRNAs in dendritic spines have been implicated in synapse remodeling or synaptic plasticity. TLS (translocated in liposarcoma), previously identified as a component of hnRNP complexes, unexpectedly showed somatodendritic localization in mature hippocampal pyramidal neurons. TLS was translocated to dendrites as an RNA-protein complex and was recruited to dendrites not only via microtubules but also via actin filaments. In mature hippocampal pyramidal neurons, TLS accumulated in the spines at excitatory postsynapses upon mGluR5 activation, which was accompanied by an increased RNA content in dendrites. Consistent with the in vitro studies, TLS-null hippocampal pyramidal neurons exhibited abnormal spine morphology and lower spine density. We further demonstrated that TLS-null neuronal dendrites had decreased RNA cargo following mGluR-activation compared to wild-type dendrites and specifically identified an actin-stabilizing protein, Nd1-L, as a TLS-associated RNA cargo. TLS participates in mRNA sorting to the dendritic spines induced by mGluR5 activation and regulates spine morphology to stabilize the synaptic structure probably through actin-network, suggesting that TLS is necessary for spine maturation and the plasticity of excitatory postsynaptic sites.

神经元树突与树突棘一起表现出非常多样的结构。树突棘中mRNA的选择性靶向和局部翻译与突触重塑或突触可塑性有关。TLS（易位在脂肪肉瘤），以前确定为hnRNP复合物的一个组成部分，出乎意料地显示体树突定位在成熟的海马锥体神经元。TLS作为RNA-蛋白质复合物被转运到树突，并且不仅通过微管而且通过肌动蛋白丝被募集到树突。在成熟的海马锥体神经元中，TLS积累在兴奋性突触后的棘mGluR 5激活后，这是伴随着树突中的RNA含量增加。与体外研究一致，TLS无效的海马锥体神经元表现出异常的棘形态和较低的棘密度。我们进一步证明，与野生型树突相比，在mGluR激活后，TLS无效神经元树突的RNA货物减少，并特别鉴定了一种肌动蛋白稳定蛋白Nd 1-L作为TLS相关的RNA货物。TLS参与mGluR 5激活诱导的树突棘的mRNA分选，并可能通过肌动蛋白网络调节树突棘的形态以稳定突触结构，提示TLS对树突棘的成熟和兴奋性突触后位点的可塑性是必需的。

项目成果

Transcriptional oscillation of canonical clock genes in mouse peripheral tissues

• DOI: 10.1186/1471-2199-5-18
• 发表时间: 2004-10-09
• 期刊: BMC MOLECULAR BIOLOGY
• 作者: Yamamoto, T;Nakahata, Y;Takumi, T
• 通讯作者: Takumi, T

Y.Kajimoto, O.Shirakawa, X.-H.Lin, T.Hashimoto, N.Kitamura, N.Murakami, T.Takumi, K.Maeda: "Synapse-associated protein 90/postsynaptic density-95-asssociated protein (SAPAP) is expressed differentially in phencyclidine-treated rats and is increased in the

Y.Kajimoto、O.Shirakawa、X.-H.Lin、T.Hashimoto、N.Kitamura、N.Murakami、T.Takumi、K.Maeda：“突触相关蛋白 90/突触后密度 95 相关蛋白（

Synapse-associated protein 90/postsynaptic density-95-asssociated protein (SAPAP) is expressed differentially in phencyclidine-freated rats and is increased in the nucleus accumbens of patients with schizophirenia.

突触相关蛋白 90/突触后密度 95 相关蛋白 (SAPAP) 在未服用苯环己哌啶的大鼠中表达差异，并且在精神分裂症患者的伏核中表达增加。

• 发表时间: 2003
• 期刊: Neuropsychopharamacology 28
• 作者: Kajimoto Y;Shirakawa O;Lin X.-H;Hashimoto T;Kitamura N;Murakami N;Takumi T;Maeda k
• 通讯作者: Maeda k

Fezl is layer-specifically expressed in the adult mouse neocortex

Fezl 在成年小鼠新皮质中层特异性表达

• 发表时间: 2004
• 期刊: Eur J Neurosci. 20
• 作者: Inoue K;Terashima T;Nishikawa T;Takumi T.
• 通讯作者: Takumi T.

Domain Architectures and characterization of an RNA-binding protein, TLS

• DOI: 10.1074/jbc.m408552200
• 发表时间: 2004-10-22
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Iko, Y;Kodama, TS;Morikawa, K
• 通讯作者: Morikawa, K