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

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15590285
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Osaka Bioscience Institute
• Principal Investigator: TAKUMI Toru Osaka Bioscience institute, Laboratory of Neuroscience, Head, 神経科学部門, 研究室長 (00222092)
• Project Period (FY): 2003 – 2004
• 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

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.

Research Products

• [Journal Article] Domain architectures and characterization of an RNA binding protein, TLS. (2004)
  • Author(s): Iko Y, Kodama TS, Kasai N, Oyama T, Morita EH, Muto T, Okumura M, Fujii R, Takumi T, Tate S, Morikawa K
  • Journal Title: J. Biol. Chem. 279
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The receptor tyrosine kinase Ror2 associates with and is activated by casein kinase Iε. (2004)
  • Author(s): Kani S, Sishi I, Yamamoto H, Yoda A, Suzuki H, Nomachi A, Iozumi K, Nishita M, Kikuchi A, Takumi T, Minami Y
  • Journal Title: J. Biol. Chem. 279
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Fez1 is layer-specificlly expressed in the adult mouse neocortex. (2004)
  • Author(s): Inoue K, Terashima T, Nishikawa T, Takumi T
  • Journal Title: Eur. J. Neurosci. 20
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transcriptional oscillation of canonical clock genes in mouse peripheral tissues. (2004)
  • Author(s): Yamamoto T, Nakahata Y, Soma H, Akashi M, Mamine T, Takumi T
  • Journal Title: BMC Mol. Biol. 5
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Domain architectures and characterization of an RNA binding protein, TLS. (2004)
  • Author(s): Iko Y, Kodama TS, Kasai N, Oyama T, Morita EH, Muto T, Okumura M, Fujii R, Takumi T, Tate S, Morikawa K
  • Journal Title: J.Biol.Chem. 279 Pages: 44834-44840
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The receptor tyrosine kinase Ror2 associates with and is activated by casein kinase I. (2004)
  • Author(s): Kani S, Oishi I, Yamamoto H, Yoda A, Suzuki H, Nomachi A, Iozumi K, Nishita M, Kikuchi A, Takumi T, Minami Y
  • Journal Title: J.Biol.Chem. 279 Pages: 50102-50109
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Fez1 is layer-specifically expressed in the adult mouse neocortex. (2004)
  • Author(s): Inoue K, Terashima T, Nishikawa T, Takumi T
  • Journal Title: Eur.J.Neurosci. 20 Pages: 2909-2916
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transcriptional oscillation of canonical clock genes in mouse peripheral tissues. (2004)
  • Author(s): Yamamoto T, Nakahata Y, Soma H, Akashi M, Mamine T T, Takumi T
  • Journal Title: BMC Mol.Biol. 5 Pages: 18
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] 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. (2003)
  • Author(s): Kajimoto Y, Shirakawa O, Lin X.-H, Hashimoto T, Kitamura N, Murakami N, Takumi T, Maeda k
  • Journal Title: Neuropsychopharamacology 28
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Synapse-associated protein 90/postsynaptic density-95-asssociated protein (SAPAP) is expressed differentially in phencyclidine-treated rats and is increased in the nucleus accumbens of patients with schizophrenia. (2003)
  • Author(s): Y.Kajimoto, O.Shirakawa, X.-H.Lin, T.Hashimoto, N.Kitamura, N.Murakami, T.Takumi, K.Maeda
  • Journal Title: Neuropsychopharamacology 28 Pages: 1831-1839
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The RNA binding protein TLS is translocated to the dendritic spines by mGluR5 activation and regulates spine morphogenesis.
  • Author(s): Fujii R, Okabe S, Urashido T, Inoue K, Yoshimura A, Tachibana T, Nishikawa T, Hicks GG, Takumi T
  • Journal Title: Curr. Biol.
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The RNA binding protein TLS is translocated to the dendritic spines by mGluR5 activation and regulates spine morphogenesis.
  • Author(s): Fujii R, Okabe S, Urushido T, Inoue K, Yoshimura A, Tachibana T, Nishikawa T, Hicks GG, Takumi T
  • Journal Title: Curr.Biol. (In press.)
  • Description: 「研究成果報告書概要(欧文)」より