Identification and characterization of proteins whose mRNAs are localized in postsynaptic region.

• Project/Area Number: 17500252
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Shinshu University
• Principal Investigator: SUZUKI Tatsuo Shinshu University, Graduate School of Medicine, Professor, 大学院医学研究科, 教授 (80162965)
• Co-Investigator(Kenkyū-buntansha): TIAN Qing Bao Shinshu University, Graduate School of Medicine, Assistant professor, 大学院医学研究科, 講師 (40324264)
• Project Period (FY): 2005 – 2006
• Project Status: Completed (Fiscal Year 2006)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: PSD / dendritic mRNA / novel gene / synapse / postsynaptic density / synaptic plasticity / memory and learning / neuronal diseases / LRP4 / postsynaptic density / lipid raft / calmodulin kinase II / cluster formation / gene chip / local protein synthesis / synaptic plastcity / molecular mechanism

Research Abstract

We cloned various novel genes of which mRNAs are localized in the postsynaptic compartments, and which are translated and targeted to postsynaptic sites. We further characterized their nature and functions in vivo.
1. We produced targeting vectors for LRP4 (LDL receptor-related protein 4) and synUSP (synaptic Ubiquitin-specific protease). We continue to make knockout mice for these genes. We identified apoE as a ligand for LRP4. In addition, we also identified another LRP4 ligand and suggested a. role of LRP4 in axon guidance.
2. Using antibody towards ligand-binding domain of LRP4, we suggested that LRP4 is involved in synaptic differentiation and neuronal survival.
3. We analyzed mRNA species that are associated with postsynaptic density (PSD) fraction by using gene chip microarray. In the study we identified about 1,900 mRNA species that are highly concentrated to the PSD fraction. We also identified localization of neuronal disease-related mRNAs at the postsynaptic site.
4. We demonstrated at the electron microscopic level that p55 protein is localized to PSD.
5. We characterized IQ-ArfGEF/BRAG1, which is closely related to aynArfGEF/BRAG3.
6. We found that cluster formation of CaMKII occurs in lipid raft microdomains.

Research Products

• [Journal Article] Characterization of mRNA species that are associated with postsynaptic density fraction by gene chip microarray analysis. (2007)
  • Author(s): Suzuki T, Tian QB, Kuromitsu J, Kawai T, Endo S
  • Journal Title: Neurosci.Res. 57 Pages: 61-85
  • NAID: 10021188121
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] シナプス構築におけるMAGUKファミリータンパクp55の関与 (2007)
  • Author(s): 鈴木龍雄, Chiye Aoki
  • Journal Title: 生体の科学 58 Pages: 108-112
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Characterization of mRNA species that are associated with postsynaptic density fraction by gene chip microarray analysis. (2007)
  • Author(s): Suzuki T, Tian QB, Kromitsu J, Kawai T, Endo S
  • Journal Title: Neurosci Res 57 Pages: 61-85
  • NAID: 10021188121
• [Journal Article] シナプス構築におけるMAGUKファミリータンパクp55の関与 (2007)
  • Author(s): 鈴木龍雄, Chiye Aoki
  • Journal Title: 生体の科学 58(印刷中)
• [Journal Article] Interaction of LDL receptor-related protein 4 (LRP4) with postsynaptic scaffold proteins via its C-terminal PDZ domain-binding motif, and its regulation by Ca^<2+>/calmodulin-dependent protein kinase II. (2006)
  • Author(s): Tian Q-B., Suzuki T., Yamauchi T., Sakagami H., Yoshimura Y., Miyazawa S., Nakayama K., Saitoh F., Zhang J-P., Kondo H., Endo S.
  • Journal Title: Eur J Neurosci. 23 Pages: 2864-2876
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mechanisms for association of Ca2+/calmodulin-dependent protein kinase II with lipid rafts. (2006)
  • Author(s): Du F, Saitoh F, Tian QB, Miyazawa S, Endo S, Suzuki T
  • Journal Title: Biochem.Biophys.Res.Commun. 347 Pages: 814-820
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Interaction of LDL receptor-related protein 4 (LRP4) with postsynaptic scaffold proteins via its C-terminal PDZ domain-binding motif; and its regulation by Ca^<2+>/calmodulin-dependent protein kinase (2006)
  • Author(s): Tian Q-B., Suzuki T., Yamauchi T., Sakagami H., Yoshimura Y., Miyazawa S., Nakayama K., Saitoh F., Zhang J-P., Kondo H., Endo S.
  • Journal Title: Eur J Neurosci. 23 Pages: 2864-2876
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mechanisms for association of Ca^<2+>/calmodulin-dependent protein kinase II with lipid rafts (2006)
  • Author(s): Du F, Saitoh F, Tian QB, Miyazawa S, Endo S, Suzuki T
  • Journal Title: Biochem. Biophys. Res. Commun. 347 Pages: 814-820
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Characterization of mRNA species that are associated with postsynaptic density fraction by gene chip microarray analysis (2006)
  • Author(s): Suzuki T, Tian QB, Kuromitsu J, Kawai T, Endo S
  • Journal Title: Neurosci. Res. 57 Pages: 61-85
  • NAID: 10021188121
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mechanisms for association of Ca2+/calmodulin-dependent protein kinase II with lipid rafts. (2006)
  • Author(s): Du F, Saitoh F, Tian QB, Miyazawa S, Endo S, Suzuki T
  • Journal Title: Biochem Biophys Res Commun. 347 Pages: 814-820
• [Journal Article] Interaction of LDL receptor-related protein 4 (LRP4) with postsynaptic scaffold proteins via its C-terminal PDZ domain-binding motif, and its regulation by Ca^<2+>/calmodulin-dependent protein kinase II. (2006)
  • Author(s): Tian Q-B., Suzuki T., Yamauchi T., Sakagami H., Yoshimura Y., Miyazawa S., Nakayama K., Saitoh F., Zhang J-P., Kondo H., Endo S.
  • Journal Title: Eur J Neurosci (in press)
• [Journal Article] BAALC 1-6-8 protein is targeted to postsynaptic lipid rafts by its N-terminal miristoylation and palmitoylation, and interacts with α,but not β, subunit of Ca2+/calmodulin-dependent protein kinase II (2005)
  • Author(s): Wang X., Tian Q-B., Okano A., Sakagami H., Moon Il., Kondo H., Endo S., Suzuki T.
  • Journal Title: J.Neurochem 92 Pages: 674-659
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A novel scaffold protein, TANC, possibly a rat homolog of Drosophila rolling pebbles (rols), forms a multi-protein complex with various postsynaptic density proteins (2005)
  • Author(s): Suzuki T., Li W., Zhang J-P., Tian Q-B., Sakagami H., Usuda N., Kondo H., Fujii T., Endo S.
  • Journal Title: Eur.J.Neurosci. 21 Pages: 339-350
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] p55 protein is a member of PSD scaffold proteins in the rat brain and interacts with various PSD proteins (2005)
  • Author(s): Zhang J-P., Tian Q-B., Sakagami H., Endo S., Kondo H., Suzuki T.
  • Journal Title: Mol.Brain Res. 135 Pages: 204-216
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] シナプス分子と精神・神経疾患 (2005)
  • Author(s): 鈴木龍雄
  • Journal Title: 基礎老化研究 29 Pages: 11-15
  • NAID: 10027835569
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] BAALC 1-6-8 protein is targeted to postsynaptic lipid rafts by its N-terminal mirystoylation and palmitoylation, and interacts with α, but not β, subunit of Ca^<2+>/calmodulin-dependent protein kinase II (2005)
  • Author(s): Wang X., Tian Q-B., Okano A., Sakagami H., Moon Il., Kondo H., Endo S., Suzuki T.
  • Journal Title: J. Neurochem. 92 Pages: 674-659
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A novel scaffold protein, TANC, possibly a rat homolog of Drosophila rolling pebbles (rols), forms a multi-protein complex with various postsynaptic density proteins (2005)
  • Author(s): Suzuki T., Li W., Zhang J-P., Tian Q-B., Sakagami H., Usuda N., Kondo H., Fujii T., Endo S
  • Journal Title: Eur. J. Neurosci. 21 Pages: 339-350
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] p55 protein is a member of PSD scaffold proteins in the rat brain and interacts with various PSD proteins (2005)
  • Author(s): Zhang J-P., Tian Q-B., Sakagami H., Endo S., Kondo H., Suzuki T.
  • Journal Title: Mol. Brain Res. 135 Pages: 204-216
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] BAALC 1-6-8 protein is targeted to postsynaptic lipid rafts by its N-terminal miristoylation and palmitoylation, and interacts with a, but not b, subunit of Ca2+/calmodulin-dependent protein kinase II. (2005)
  • Author(s): Wang X., Tian Q-B., Okano A., Sakagami H., Moon II, Kondo H., Endo S., Suzuki T.
  • Journal Title: J.Neurochem. 92 Pages: 674-659
• [Journal Article] A novel scaffold protein, TANC, possibly a rat homolog of Drosophila, rolling pebbles (rols), forms a multi-protein complex with various postsynaptic density proteins. (2005)
  • Author(s): Suzuki T., Li W., Zhang J-P., Tian Q-B., Sakagami H., Usuda N., Kondo H., Fujii T., Endo S.
  • Journal Title: Eur.J.Neurosci 21 Pages: 339-350
• [Journal Article] p55 protein is a member of PSD scaffold proteins in the rat brain an interacts with various PSD proteins. (2005)
  • Author(s): Zhang J-P., Tian Q-B., Sakagami H., Endo S., Kondo H., Suzuki T.
  • Journal Title: Mol.Brain Res. 135 Pages: 204-216