Functional analysis of novel membrane protein network at the synapse

• Project/Area Number: 18700376
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: National Institute for Physiological Sciences (2007-2008); National Institute for Longevity Sciences,NCGG (2006)
• Principal Investigator: FUKATA Yuko National Institute for Physiological Sciences, 細胞器官研究系, 准教授 (40416186)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,810,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2007: ¥1,400,000 (Direct Cost: ¥1,400,000); Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
• Keywords: 膜蛋白質 / 蛋白質複合体 / 神経シナプス / 神経科学 / 生化学 / てんかん / 質量分析 / グルタミン酸受容体

Research Abstract

膜蛋白質は細胞外シグナルを正確に認識し、細胞内に情報を伝達する。膜蛋白質は単独で機能するのではなく、様々な蛋白質と複合体を形成して、その機能、局在が正確に制御されている。本研究では神経シナプス膜において重要な役割を担う足場蛋白質PSD-95を含む新規シナプス膜蛋白質複合体として、てんかん関連リガンド・受容体LGI1・ADAM22を発見し、新たなシナプス伝達制御機構を明らかにした(Fukata Y et al, Science 2006)。

Research Products

• [Journal Article] Dynamic protein palmitoylation in cellular signaling. (2009)
  • Author(s): Iwanaga, T., Tsutsumi, R., Noritake, J., Fukata, Y., Fukata, M.
  • Journal Title: rog Lipid Res (in press)
  • Peer Reviewed
• [Journal Article] The Hydrophobic cysteine-rich domain of SNAP25 couples with downstream residues to mediated membrane interactions and recognitions by DHHC palmitoyl transferases. (2009)
  • Author(s): Greaves, J., Prescott, G.R., Fukata, Y., Fukata, M., Salaun, C., Chamberlain, L.H.
  • Journal Title: Mol. Biol. Cell 20 Pages: 1845-1854
  • Peer Reviewed
• [Journal Article] Identification of G-protein alpha subunit palmitoylating enzyme. (2009)
  • Author(s): Tsutsumi, R., Fukata, Y., Noritake, J., Iwanaga, T., Perez, F., Fukata, M.
  • Journal Title: Mol. Cell. Biol. 29 Pages: 435-447
  • Peer Reviewed
• [Journal Article] The Hydrophobic cysteine-rich domain of SNAP25 couples with downstream residues to mediated membrane interactions and recognitions by DHHC palmitoyl transferases (2009)
  • Author(s): Greaves, J., et.al.
  • Journal Title: Mol. Biol. Cell 20 Pages: 1845-1854
  • Peer Reviewed
• [Journal Article] Identification of G-protein alpha subunit palmitoylating enzyme (2009)
  • Author(s): Tsutsumi, R., et.al.
  • Journal Title: Mol. Cell. Biol. 29 Pages: 435-447
  • Peer Reviewed
• [Journal Article] Dynamic protein palmitoylation in cellular signaling (2009)
  • Author(s): Iwanaga, T., et.al.
  • Journal Title: Prog Lipid Res. (In press)
  • Peer Reviewed
• [Journal Article] Discovery of protein-palmitoylating enzymes. (2008)
  • Author(s): Tsutsumi, R., Fukata, Y., Fukata, M.
  • Journal Title: Pflugers Arch-Eur. J. Physiol. 456 Pages: 1199-1206
  • Peer Reviewed
• [Journal Article] Fibroblast Growth Factor-Regulated Palmitoylation of NCAM Determines Neuronal Morphogenesis. (2008)
  • Author(s): Ponimaskin, E., Dityateva, G., Ruonala, M., Fukata, M., Fukata, Y., Kobe, F., Wouters, F., Delling, M., Bredt, D., Schachner, M., Dityatev, A.
  • Journal Title: J. Neurosci. 28 Pages: 88897-88907
  • Peer Reviewed
• [Journal Article] DHHC proteins regulate stable membrane binding of the molecular chaperone cysteine-string protein. (2008)
  • Author(s): Greaves, J., Salaun, C., Fukata, Y., Fukata, M., Chamberlain, L.H.
  • Journal Title: J. Biol. Chem. 283 Pages: 25014-25026
  • Peer Reviewed
• [Journal Article] Fibroblast Growth Factor-Regulated Palmitoylation of NCAM Determines Neuronal Morohogenesis (2008)
  • Author(s): Ponimaskin, E., et.al.
  • Journal Title: J. Neurosci. 28 Pages: 88897-88907
  • Peer Reviewed
• [Journal Article] Discovery of protein-palmitoylating enzymes (2008)
  • Author(s): Tsutsumi, R., et.al.
  • Journal Title: Pflugers Arch-Eur. J. Physiol. 456 Pages: 1199-1206
  • Peer Reviewed
• [Journal Article] DHHC proteins regulate stable membrane binding of the molecular chaperone cysteine-string protein (2008)
  • Author(s): Greaves, J., et.al.
  • Journal Title: J. Biol. Chem. 283 Pages: 25014-25026
  • Peer Reviewed
• [Journal Article] Discovery of protein-palmitoylating enzymes. (2008)
  • Author(s): Tsutsumi, R., et. al.,
  • Journal Title: Pflugers Arch-Eur. J. Physiol (in press)
  • Peer Reviewed
• [Journal Article] GM1-ganglioside-induced Aβassembly at synaptic sites of cultured neurons. (2007)
  • Author(s): Yamamoto, N., Fukata, Y., Fukata, M., Yanaigiswa, K.
  • Journal Title: Biochim Biophys Acta 1768 Pages: 1128-1137
  • Peer Reviewed
• [Journal Article] Stargazin interacts functionally with the AMPA receptor glutamate-binding module. (2007)
  • Author(s): Tomita, S., Shenoy, A., Fukata, Y., Nicoll, R.A., Bredt, D.S.
  • Journal Title: Neuropharmacology 52 Pages: 87-91
  • Peer Reviewed
• [Journal Article] GM1-genglioside-induced Aβ assembly at synaptic sites of cultured neurons. (2007)
  • Author(s): Yamamoto, N., et. al.,
  • Journal Title: Biochim Biophys Acta 1768 Pages: 1128-1137
  • Peer Reviewed
• [Journal Article] GM1-ganglioside-induced Aβ assembly at synaptic sites of cultured neurons. (2007)
  • Author(s): Yamamoto, N. et al.
  • Journal Title: Biochim. Biophys. Acta. (In press)
• [Journal Article] Stargazin interacts functionally with the AMPA receptor glutamate-binding module. (2007)
  • Author(s): Tomita, S. et al.
  • Journal Title: Neuropharm. 52 Pages: 87-91
• [Journal Article] GODZ-mediated palmitoylation of GABA-A receptors is required for normal assembly and function of GABAergic inhibitory synapses. (2006)
  • Author(s): Fang, C., Deng, L., Keller, C., Fukata, M., Fukata, Y., Chen G., Luscher, B.
  • Journal Title: J Neurosci. 26 Pages: 12758-12768
  • Peer Reviewed
• [Journal Article] Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulates synaptic transmission. (2006)
  • Author(s): Fukata Y., Adesnik H., Iwanaga T., Bredt D.S., Nicoll R.A., Fukata M.
  • Journal Title: Science 313 Pages: 1792-1795
  • Peer Reviewed
• [Journal Article] Systematic screening for palmitoyl transferase activity of the DHHC protein family in mammalian cells. (2006)
  • Author(s): Fukata, Y., Iwanaga, T., Fukata, M.
  • Journal Title: Methods 40 Pages: 177-182
  • Peer Reviewed
• [Journal Article] Identification of Golgi-localized acyl transferases that palmitoylate and regulate endothelial nitric oxide synthase. (2006)
  • Author(s): Fernandez-Hernando, C., Fukata, M., Bernatchez, P.N., Fukata, Y., Lin, M.I., Bredt, D.S., Sessa, W.C.
  • Journal Title: J. Cell Biol. 174 Pages: 369-377
  • Peer Reviewed
• [Journal Article] Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulates synaptic transmission. (2006)
  • Author(s): Fukata Y., et al.
  • Journal Title: Science 313 Pages: 1792-1795
• [Journal Article] Systematic screening for palmitoyl transferase activity of the DHHC protein family in mammalian cells. (2006)
  • Author(s): Fukata, Y. et al.
  • Journal Title: Methods 40 Pages: 177-182
• [Journal Article] Identification of Golgi-localized acyl transferases that palmitoylate and regulate endothelial nitric oxide synthase. (2006)
  • Author(s): Fernandez-Hernando, C., et al.
  • Journal Title: J. Cell Biol. 174 Pages: 369-377
• [Journal Article] GODZ-meaiated palmitoytation of GABA-A receptors is required for normal assembly and function of GABAergic inhibitory synapses. (2006)
  • Author(s): Fang, C. et al.
  • Journal Title: J. Neurosci. 26 Pages: 12758-12768
• [Presentation] In vivo function of epilepsy-related ligand LGI1. (2009)
  • Author(s): Fukata, Y.
  • Organizer: 11th International Neurochemistry Winter Conference
  • Place of Presentation: Solden, Austria
  • Year and Date: 2009-03-31
• [Presentation] Synaptic palmitoylation of PSD-95 mediates AMPA receptor homeostasis (2009)
  • Author(s): 深田正紀ら
  • Organizer: 11th International Neurochemistry Winter Conference
  • Place of Presentation: Solden, Austria
  • Year and Date: 2009-03-31
• [Presentation] In. vivo function of epilepsy-related ligand LGI1 (2009)
  • Author(s): 深田優子ら
  • Organizer: 11th International Neurochemistry Winter Conference
  • Place of Presentation: SOLDEN, Austria
  • Year and Date: 2009-03-31
• [Presentation] Synaptic palmitoylation of PSD-95 mediates AMPA receptor homeostasis (2008)
  • Author(s): 深田正紀ら
  • Organizer: The 48th American Society for Cell Biology An nual Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2008-12-14
• [Presentation] シナプス伝達修飾分子LGIファミリーの性状解析 (2008)
  • Author(s): 岩永剛ら
  • Organizer: 第31回日本分子生物学会、第81回日本生化学会大会合同大会BMB2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] Gαパルミトイル化酵素の同定と性状解析 (2008)
  • Author(s): 堤良平ら
  • Organizer: 第31回日本分子生物学会、第81回日本生化学会大会合同大会BMB2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Activity-Dependent Regulation of the PSD-95 Palmitoylating Enzyme (2008)
  • Author(s): 則竹淳ら
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2008-07-10
• [Presentation] Synaptic activity regulates PSD-95 palmitoylating enzymes (2008)
  • Author(s): 深田正紀ら
  • Organizer: The 8th Human Frontier Science Program Awardees Meeting
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-07-08
• [Presentation] Identification of the epilepsy-related LGI1 multiprotein complex (2008)
  • Author(s): 深田優子
  • Organizer: 第38回生理研国際シンポジウム
  • Place of Presentation: 岡崎
  • Year and Date: 2008-03-18
• [Presentation] Activity-dependent regulation of PSD-95 palmitoylating enzymes (2008)
  • Author(s): 則竹淳, ら
  • Organizer: 第38回生理研国際シンポジウム
  • Place of Presentation: 岡崎
  • Year and Date: 2008-03-18
• [Presentation] Physiological role of epilepsy-related ligand LGI1 in synaptic function (2008)
  • Author(s): Fukata, Y.
  • Organizer: The 48th American Society for Cell Biology Annual Meeting
  • Place of Presentation: San Francisco, USA
• [Presentation] Identification of the epilepsy-related LGI1 multiprotein complex. (2008)
  • Author(s): Fukata, Y.
  • Organizer: The 36th SEIRIKEN Conference "Stock and Flow of functional molecules in synapse"
  • Place of Presentation: Okazaki, Japan
• [Presentation] PSD-95パルミトイル化酵素の活性制御機構の解明 (2007)
  • Author(s): 深田正紀, ら
  • Organizer: 第30回日本分子生物学会、第80回日本生化学会大会合同大会BMB2007
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-15
• [Presentation] 新規リガンドLGIファミリーの神経系における機能 (2007)
  • Author(s): 深田優子
  • Organizer: 第30回日本分子生物学会年回、第80回日本生化学会大会合 同大会BMB2007
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] 新規リガンドLGIファミリーの神経系における機能 (2007)
  • Author(s): 深田優子
  • Organizer: 第30回日本分子生物学会、第80回日本生化学会大会合同大会BMB2007
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] Regulation of Gα palmitoylation by DHHC family proteins (2007)
  • Author(s): 堤良平, ら
  • Organizer: The 47th Annual Meeting of American Society for Cell Biology
  • Place of Presentation: Washington DC, USA.
  • Year and Date: 2007-12-14
• [Presentation] Regulatory Mechanism of PSD-95 Palmitoylation through P-PAT (2007)
  • Author(s): 則竹淳, ら
  • Organizer: The Annual Meeting of Society for Neuroscience
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2007-11-05
• [Presentation] PSD-95パルミトイル化酵素によるAMPA受容体の動態制御機構 (2007)
  • Author(s): 深田正紀, ら
  • Organizer: 第54回中部日本生理学会、第100回近畿生理学談話会 合同大会
  • Place of Presentation: 津
  • Year and Date: 2007-10-19
• [Presentation] 新規リガンド・受容体LGI1/ADAM22によるシナプス機能制御 (2007)
  • Author(s): 深田優子
  • Organizer: 生理学研究所研究会「シナプス可塑性の分子的基盤」
  • Place of Presentation: 岡崎
• [Presentation] Novel epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulates synaptic transmission. (2006)
  • Author(s): Fukata, Y.
  • Organizer: The 46th Annual Meeting of American Society for Cell Biology
  • Place of Presentation: San Diego, USA
• [Book] 生化学(Short Review「タンパク質S-パルミトイル化酵素」, 80) (2008)
  • Author(s): 堤良平、深田優子、深田正紀
  • Publisher: 日本生化学学会
• [Book] 日本神経薬理学会雑誌(AMPA型グルタミン酸受容体の動態制御機構, 28) (2008)
  • Author(s): 深田優子、深田正紀
• [Book] 蛋白質核酸酵素(「PSD-95 パルミトイル化脂質修飾酵素によるAMPA受容体動態制御メカニズム」「神経の分化、回路形成、機能発現」, 増刊号, 53(4)) (2008)
  • Author(s): 則竹淳、深田優子、深田正紀
  • Publisher: 共立出版
• [Book] 生化学 (2008)
  • Author(s): 堤良平ら
  • Publisher: 日本生化学学会
• [Book] AMPA型グルタミン酸受容体の動態制御機構 (2008)
  • Author(s): 深田優子ら
  • Publisher: 日本神経薬理学会雑誌
• [Book] 「神経の分化、回路形成、機能発現」PSD-95パルミトイル化脂質修飾酵素によるAMPA受容体動態制御メカニズム (2008)
  • Author(s): 則竹淳, ら
  • Publisher: 蛋白質核酸酵素
• [Book] 蛋白質核酸酵素(Short Review「てんかん関連蛋白質LGI1はシナプス伝達を制御する」, 52) (2007)
  • Author(s): 深田優子、岩永剛、深田正紀
  • Publisher: 共立出版
• [Book] てんかん関連蛋白質LGI1はシナプス伝達を制御する (2007)
  • Author(s): 深田優子, ら
  • Publisher: 蛋白質核酸酵素
• [Book] 細胞工学(Hot Press「てんかん関連蛋白質"LGI1とADAM22"はリガンド/受容体としてシナプス伝達を制御する」, 12月号 25) (2006)
  • Author(s): 深田優子、岩永剛、深田正紀
  • Publisher: 羊土社
• [Book] Protein palmitoylation by DHHC protein family.(The Dynamic Synapse: Molecular Methods in Ionotropic Receptor Biology.) (2006)
  • Author(s): Fukata, Y., Bredt, DS., Fukata, M.
  • Publisher: CRC Press
• [Book] The Dynamic Synapse : Molecular Methods in Ionotropic Receptor Biology. Protein palmitoylation by DHHC protein family. (2006)
  • Author(s): Fukata, Y. et al.
  • Publisher: The CRC Press
• [Remarks]
  • URL: http://www.nips.ac.jp/fukata/
• [Remarks] 新聞発表 日本経済新聞(平成18年9月22日朝刊)「脳神経制御するたんぱく質発見」など
• [Remarks]
  • URL: http://www.nips.ac.jp/fukata/
• [Remarks]
  • URL: http://www.nips.ac.jp/fukata/