| Project/Area Number |
15590285
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
TAKUMI Toru Osaka Bioscience institute, Laboratory of Neuroscience, Head, 神経科学部門, 研究室長 (00222092)
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| Co-Investigator(Kenkyū-buntansha) |
藤井 律子 (財)大阪バイオサイエンス研究所, 神経科学部門, 研究員 (90342716)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | 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 |
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| Research Abstract |
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.
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