Functional roles of PKC-dependent SNAP-25 phosphorylation in brain function

• Project/Area Number: 18300127
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kitasato University
• Principal Investigator: TAKAHASHI Masami Kitasato University, 医学部, 教授 (10318826)
• Co-Investigator(Kenkyū-buntansha): ITAKURA Makoto 北里大学, 医学部, 講師 (30398581) ; AZUMA Sadahiro 北里大学, 医学部, 助教 (80348507) ; KATAOKA Masakazu 信州大学, 工学部, 准教授 (90332676)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,380,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥2,580,000); Fiscal Year 2008: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2007: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2006: ¥6,200,000 (Direct Cost: ¥6,200,000)
• Keywords: 神経伝達物質 / SNAREタンパク質 / 開口放出 / シナプス前性制御 / タンパク質リン酸化 / ストレス / SNAP-25 / プロテインキナーゼC / ノックインマウス / アドレナリン / 情動異常

Research Abstract

SNAP-25はシナプス前部に発現するタンパク質で、神経伝達物質の放出に必須な役割を果たしている。SNAP-25のSer187はプロテインキナーゼCによってリン酸化を受けるが、その機能的な役割については明らかではなかった。今回プロテインキナーゼCによる神経伝達物質の放出制御にそのリン酸化が必須であり、ストレス応答などの脳機能や、てんかん発作など疾患に深く関わっていることを明らかにした。

Research Products

• [Journal Article] Identification of a minimal segment of complexin II essential for preferential distribution in axons (2009)
  • Author(s): Kataoka M, Sekiguchi M, Takahashi M.
  • Journal Title: J Neurochem 108 Pages: 1109-1115
  • Peer Reviewed
• [Journal Article] Identification of a minimal segment of complexin II essential for preferential distribution in axons. (2009)
  • Author(s): Kataoka M, 高橋正身, 他
  • Journal Title: J Neurochem 108 Pages: 1109-1115
  • Peer Reviewed
• [Journal Article] Activity-dependent phosphorylation of Ser^<187> is required for SNAP-25-negative modulation of neuronal voltage-gated calcium channels (2008)
  • Author(s): Pozzi D, Condliffe S, Bozzi Y, Chikhladze M, Grumelli C, Proux-Gillardeaux V, Takahashi M, Franceschetti S, Verderio C, Matteoli M.
  • Journal Title: Proc Natl Acad Sci U S A 105 Pages: 323-328
  • Peer Reviewed
• [Journal Article] Phosphorylation of SNAP-25 at Ser187 mediates enhancement of exocytosis by a phorbol ester in INS-1 cells (2008)
  • Author(s): Shu Y, Liu X, Yang Y, Takahashi M, Gillis KD
  • Journal Title: J Neurosci 28 Pages: 21-23
  • Peer Reviewed
• [Journal Article] Left-right asymmetry of the hippocampal synapses with differential subunit allocation of glutamate receptors (2008)
  • Author(s): Shinohara Y, Hirase H, Watanabe M, Itakura M, Takahashi M, Shigemoto R
  • Journal Title: Proc Natl Acad Sci U S A 105 Pages: 19498-503
  • Peer Reviewed
• [Journal Article] Activity-dependent phosphorylation of Ser187 is required for SNAP-25-negative modulation of neuronal voltage-gated calcium channels. (2008)
  • Author(s): Pozzi D, 高橋正身, 他
  • Journal Title: Proc Natl Acad Sci U S A 105 Pages: 323-328
  • Peer Reviewed
• [Journal Article] Phosphorylation of SNAP-25 at Serl87 mediates enhancement of exocytosis by a phorbol ester in INS-l cells. (2008)
  • Author(s): Shu Y, 高橋正身, 他
  • Journal Title: J Neurosci 28 Pages: 21-30
  • Peer Reviewed
• [Journal Article] Left-right asymmetry of the hippocampal synapses with differential subunit allocation of glutamate receptors. (2008)
  • Author(s): Shinohara Y, 高橋正身, 他
  • Journal Title: Proc Natl Acad Sci U S A 105 Pages: 19498-19503
  • Peer Reviewed
• [Journal Article] Dual regulation of astrocyte gap junction hemichannels by growth factors and a pro-inflammatory cytokine via the mitogen-activated protein kinase cascade (2007)
  • Author(s): Morita M, Saruta C, Kozuka N, Okubo Y, Itakura M, Takahashi M, Kudo Y.
  • Journal Title: Glia 55 Pages: 508-515
  • Peer Reviewed
• [Journal Article] Phosphorylation of adult type Sept5 (CDCrel-1) by cyclin-dependent kinase 5 inhibits interaction with syntaxin-1 (2007)
  • Author(s): Taniguchi M, Taoka M, Itakura M, Asada A, Saito T, Kinoshita M, Takahashi M, Isobe T, Hisanaga SI.
  • Journal Title: J Biol Chem 282 Pages: 7869-7876
  • Peer Reviewed
• [Journal Article] Phosphomimetic mutation of Ser-187 of SNAP-25 increases both syntaxin binding and highly Ca^<2+> sensitive exocytosis (2007)
  • Author(s): Yang Y, Craig TJ. Chen X, Ciufo LF, Takahashi M, Morgan A, Gillis KD
  • Journal Title: J Gen Physiol 129 Pages: 233-244
  • Peer Reviewed
• [Journal Article] RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca^<2+> channels (2007)
  • Author(s): Kiyonaka S, Wakamori M, Miki T, Uriu Y, Nonaka M, Bito H, Beedle AM, Mori E, Hara Y, De Waard M, Kanagawa M, Itakura M, Takahashi M, Campbell KP, Mori Y.
  • Journal Title: Nat Neurosci 10 Pages: 691-701
  • Peer Reviewed
• [Journal Article] Phosphorylation of adult type Sept5 (CDCrel-1) by cyclin-dependent kinase 5 inhibits interaction with syntaxin-1 (2007)
  • Author(s): Taniguchi M
  • Journal Title: J Biol Chem 282 Pages: 7869-7876
  • Peer Reviewed
• [Journal Article] Phosphomimetic mutation of Ser-187 of SNAP-25 increases both syntaxin binding and highly Ca^<2+> sensitive exocytosis (2007)
  • Author(s): Yang Y
  • Journal Title: J Gen Physiol 129 Pages: 233-244
  • Peer Reviewed
• [Journal Article] RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca^<2+> channels (2007)
  • Author(s): Kiyonaka S
  • Journal Title: Nat. Neurosci 10 Pages: 691-701
  • Peer Reviewed
• [Journal Article] Activity-dependent phosphorylation of Ser187 is required for SNAP-25-negative modulation of neuronal voltage-gated calcium channels (2007)
  • Author(s): Pozzi D
  • Journal Title: Proc Natl Acad Sci USA 105 Pages: 323-328
  • Peer Reviewed
• [Journal Article] Phosphorylation of SNAP-25 at Ser187 mediates enhancement of exocytosis by a phorbol ester in INS-1 cells (2007)
  • Author(s): Shu Y
  • Journal Title: J Neurosci 28 Pages: 21-30
  • Peer Reviewed
• [Journal Article] Dual regulation of astrocyte gap junction hemichannels by growth factors and a pro-inflammatory cytokine via the mitogen-activated protein kinase cascade (2007)
  • Author(s): Mitsuhiro Morita
  • Journal Title: Glia 55 Pages: 508-515
• [Journal Article] Ca^<2+>-calmodulin-dependent myosin light chain kinaseis essential for activation of TRPC5 channels expressed in HEK293 cells. (2006)
  • Author(s): Shimizu S, Yoshida T, Wakamori M, Ishii M, Okada T, Takahashi M, Seto M, Sakurada K, Kiuchi Y, Mori Y
  • Journal Title: J Physiol 570.2 Pages: 219-235
  • Peer Reviewed
• [Journal Article] Differential localization and regulation of stargazin-like protein,γ-8 and stargazin in the plasma membrane of hippocampal and cortical neurons (2006)
  • Author(s): Inamura M, Itakura M, Okamoto H, Hoka S, Mizoguchi A, Fukazawa Y, Shigemoto R, Yamamori S, Takahashi M
  • Journal Title: Neurosci Res 55 Pages: 45-53
  • NAID: 10020616574
  • Peer Reviewed
• [Journal Article] Differential distributions of the Ca^<2+>-dependent activator protein for secretion family proteins (CAPS2 and CAPS1) in the mouse brain (2006)
  • Author(s): Sadakata T, Itakura M, Kozaki S, Sekine Y, Takahashi M, Furuichi T.
  • Journal Title: Comp Neurol 495 Pages: 735-753
  • Peer Reviewed
• [Journal Article] Enhanced activation of Ca^<2+>/calmodulin-dependent protein kinase II upon downregulation of cyclin-dependent kinase 5-p35 (2006)
  • Author(s): Hosokawa T, Saito T, Asada A, Ohshima T, Itakura M, Takahashi M, Fukunaga K, Hisanaga S
  • Journal Title: J. Neurosci Res 84 Pages: 747-754
  • Peer Reviewed
• [Journal Article] Development- and activity-dependent regulation of SNAP-25 phosphorylation in rat brain (2006)
  • Author(s): Kataoka M, Kuwahara R, Matsuo R, Sekiguchi M, Inokuchi K, Takahashi M
  • Journal Title: Neurosci Lett 407 Pages: 258-262
  • Peer Reviewed
• [Journal Article] Ca^<2+> channel activating action of maitotoxin in cultured brainstem neurons (2006)
  • Author(s): Kakizaki A, Takahashi M, Akagi H, Tachikawa E, Yamamoto T, Taira E, Yamakuni T, Ohizumi Y
  • Journal Title: Eur J Pharmcol 536 Pages: 223-231
  • Peer Reviewed
• [Journal Article] Differential localization and regulation of stargazin-like protein, γ-8 and stargazin in the plasma membrane of hippocampal and cortica 1 neurons (2006)
  • Author(s): Mihiko Inamura
  • Journal Title: Neurosci.Res 55 Pages: 45-53
• [Journal Article] Differential distributions of the Ca^2+dependent activator protein for secretion family protein(CAPS2 and CAPS1) in the mouse brain (2006)
  • Author(s): Tetsushi Sedataka
  • Journal Title: Comp Neurol 495 Pages: 735-754
• [Journal Article] Enhanced activation of Ca^2+/calmodulin-dependent protein kinase II upon downregulation of cyclin-dependent kinase 5-p35 (2006)
  • Author(s): Tomohisa Hosokawa
  • Journal Title: J.Neurosci. Res. 84 Pages: 747-754
• [Journal Article] Development and activity-dependent regulation of SNAP-25 phospho rylation in rat brain (2006)
  • Author(s): Masakazu Kataoka
  • Journal Title: Neurosci.Lett. 407 Pages: 258-262
• [Journal Article] Ca^2+ channel activating action of maitotoxin in cultured brainstem neurons (2006)
  • Author(s): Atsushi Kakizaki
  • Journal Title: Eur.J.Pharmcol. 536 Pages: 223-231
• [Presentation] Stress-induced phosphorylation of SNAP-25 in mouse brain. (2008)
  • Author(s): 菅谷大地, 高橋正身, 他
  • Organizer: 第51回日本神経化学会大会
  • Place of Presentation: 富山国際会議場
  • Year and Date: 2008-09-10
• [Presentation] Stargazin-like protein, γ-8 is associated with calcineurin in rat hippocampus (2008)
  • Author(s): 渡辺和泉, 高橋正身, 他
  • Organizer: Neuroscience 2008 (第31回日本神経科学大会)
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2008-07-10
• [Presentation] Neuropeptide Y is increased in the brain of Snap-25 mutant mice. (2008)
  • Author(s): 山森早織, 高橋正身, 他
  • Organizer: Neuroscience 2008 (第31回日本神経科学大会)
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2008-07-10
• [Presentation] Roles of Protein Phosphorylation in Neuronal and Glial functions (2008)
  • Author(s): M. Takahashi
  • Organizer: USA-Japan joint meeting for Glial Research, Mar.
  • Place of Presentation: Philadelphia
• [Presentation] Clocks, Around The Clock (2008)
  • Author(s): 高橋正身
  • Organizer: SNAP-25変異マウスの解析ー分子から行動へー三菱化学生命科学研究所公開セミナー
  • Place of Presentation: 東京
• [Presentation] Stargazin-like protein, □-8 is associated with calcineurin in rat hippocampus. Neuroscience 2008 (2008)
  • Author(s): 渡辺和泉、板倉誠、山森早織、高橋正身
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
• [Presentation] Neuropeptide Y is increased in the brain of Snap-25 mutant mice. Neuroscience 2008 (2008)
  • Author(s): 山森早織、内田達也、東貞宏、片岡正和、高橋正身
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
• [Presentation] Stress-induced phosphorylation of SNAP-25 in mouse brain (2008)
  • Author(s): 菅谷大地、山森早織、板倉誠、高橋正身
  • Organizer: 第51回日本神経化学会大会
  • Place of Presentation: 富山
• [Presentation] 毒素が拓いた情動異常の研究 (2007)
  • Author(s): KKRホテル(熱海)
  • Organizer: 第54回毒素シンポジウム
  • Place of Presentation: 犬鳴グランドホテル
  • Year and Date: 2007-09-06
• [Presentation] ミュータントマウスを用いたグリア細胞の活性化機構の解析 (2007)
  • Author(s): 高橋 正身
  • Organizer: 「神経・グリア回路網」サマーワークショップ
  • Place of Presentation: KKRホテル(熱海)
  • Year and Date: 2007-07-09
• [Presentation] 毒素が拓いた情動異常の研究 (2007)
  • Author(s): 高橋正身
  • Organizer: 第54回毒素シンポジウム
  • Place of Presentation: 大阪府犬鳴
• [Presentation] リン酸化によるグリア細胞の機能制御 Neuro2007 (2007)
  • Author(s): 高橋正身、板倉誠、安田圭一、菅谷津貴子
  • Organizer: 第30回日本神経科学大会、第50回日本神経化学会大会、第17回日本神経回路学会大会
  • Place of Presentation: 横浜
• [Presentation] ComplexinIIとParkinとの相互作用 Neuro2007 (2007)
  • Author(s): 兼田悠, 高橋正身, 片岡正和
  • Organizer: 第30回日本神経科学大会、第50回日本神経化学会大会、第17回日本神経回路学会大会
  • Place of Presentation: 横浜
• [Presentation] マウス脳でのSNAP-25 familyタンパク質の局在の解析 Neuro2007 (2007)
  • Author(s): 山森早織、板倉誠、菅谷大地、高橋正身
  • Organizer: 第30回日本神経科学大会、第50回日本神経化学会大会、第17回日本神経回路学会大会
  • Place of Presentation: 横浜
• [Presentation] C6グリオーマではホルボールエステルによって開口放出が抑制されるNeuro2007 (2007)
  • Author(s): 発表者(所属) : 安田圭一、板倉誠、菅谷津貴子、山森早織、高橋正身
  • Organizer: 第30回日本神経科学大会、第50回日本神経化学会大会、第17回日本神経回路学会大会
  • Place of Presentation: 横浜
• [Presentation] 電位依存性カルシウムチャネルgamma-5および7はAMPA型受容体と複合体を形成している。Neuro2007 (2007)
  • Author(s): 板倉誠、菅谷津貴子、山森早織、深谷昌弘、渡辺雅彦、高橋正身
  • Organizer: 第30回日本神経科学大会、第50回日本神経化学会大会、第17回日本神経回路学会大会
  • Place of Presentation: 横浜
• [Presentation] Kevin Campbell、森泰生錐体・桿体ジストロフィー遺伝変異RIM1による電位依存性カルシウムチャネルの機能変化解析Neuro2007 (2007)
  • Author(s): 三木崇史、清中茂樹、瓜生幸嗣、若森実、森恵美子、板倉誠、高橋正身
  • Organizer: 第30回日本神経科学大会、第50回日本神経化学会大会、第17回日本神経回路学会大会
  • Place of Presentation: 横浜
• [Presentation] アクティブゾーンタンパク質RIM1と電位依存性カルシウムチャネルの機能的相互作用 Neuro2007 (2007)
  • Author(s): 清中茂樹、木崇史、野中美央、瓜生幸嗣、若森実、森恵美子、原雄二、Michel De Waard、板倉誠、高橋正身、尾藤晴彦、Kevin Campbell、森泰生
  • Organizer: アクティブゾーンタンパク質RIM1と電位依存性カルシウムチャネルの機能的相互作用 Neuro2007
  • Place of Presentation: 横浜
• [Presentation] 神経伝達物質の放出とストレス脆弱性との関連;SNAP25遺伝子改変マウスでの検討 (2007)
  • Author(s): 鈴木映二、高橋正身
  • Organizer: 第23回日本ストレス学会学術総会
  • Place of Presentation: 東京
• [Presentation] Phosphorylation of SNAP-25, an essential protein for neurotransmitter release, is essential for the emotional homeostasis in mouse. 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress (2006)
  • Author(s): M. Kataoka, S. Yamamori, T. Sato, E. Suzuki, S. Watanabe, H. Miyaoka, S. Ikegami, R. Kuwahara, R. Suzuki-Migishima, Y. Nakahara, K. Inokuchi, Y. Kato-Fukui, S. Azuma, M. Yokoyama, and M. Takahashi.
  • Organizer: 第79回日本生化学会大会/第29回日本分子生物学会大会
  • Place of Presentation: 京都
• [Presentation] Preferential axonal localization of a presynaptic soluble protein, Complexin II. 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress (2006)
  • Author(s): H. Kaneda, M. Mori, Y. Hashimoto, M. Sekiguchi, M. Takahashi, M. Kataoka
  • Organizer: 第79回日本生化学会大会/第29回日本分子生物学会大会
  • Place of Presentation: 京都
• [Presentation] Cdk5 supresses the interaction of Septin5 (CDCre-1) with syntaxin -1A by phosphorylation. 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress (2006)
  • Author(s): M. Taniguchi, M. Taoka, M. Itakura, A. Akiko, T. Saito, M. Takahashi, T. Isobe, S. Hisanaga
  • Organizer: 第79回日本生化学会大会/第29回日本分子生物学会大会
  • Place of Presentation: 京都
• [Presentation] シナプスタンパク質SNAP-25のリン酸化部位変異マウスの解析 (2006)
  • Author(s): 高橋正身
  • Organizer: 第31回広島神経医学会研究会
  • Place of Presentation: 広島
• [Presentation] A single amino acid substitution of SNAP-25 at PKC-dependent phosphorylation site markedly increases the stress-vulnerability in mice (2006)
  • Author(s): M. Kataoka, S. Yamamori, T. Sato, E. Suzuki, S. Watanabe, H. Miyaoka, S. Ikegami, R. Kuwahara, R. Suzuki- Migishima, Y. Nakahara, I. Nihonmatsu, K. Inokuchi, Y. Kato-Fukui, S. Azuma, M. Yokoyama, and M. Takahashi
  • Organizer: 29th Japan Neuroscience Meeting Satellite Symposium. Mouse genetical manipulations as tools for understanding brain function
  • Place of Presentation: 京都
• [Presentation] 2つのアイソフォームSNAP-25a,bは脳内で異なる局在を示す (2006)
  • Author(s): 板倉誠、山森早織、高野幸太、高橋正身
  • Organizer: 第29回日本神経科学学会大会
  • Place of Presentation: 京都
• [Presentation] E. Monlnar、重本隆一凍結割断レプリカ免疫標識法を用いた海馬神経細胞膜上イオンチャネル型グルタミン酸受容体分布の高解像度解析 (2006)
  • Author(s): 深澤有吾、板倉誠、高橋正身、斉藤喜人、井ノ口馨
  • Organizer: 第29回日本神経科学学会大会
  • Place of Presentation: 京都
• [Presentation] Phorbol 12-myristate 13 acetate suppresses Ca2+-dependent peptide hormone release from astrocyte (2006)
  • Author(s): 板倉誠、安田圭一、菅谷津貴子、山森早織、高橋正身
  • Organizer: 第49回日本神経化学会大会(第28回日本生物学的精神医学会、第36回日本神経精神薬理学会)
  • Place of Presentation: 名古屋
• [Presentation] Reactive astrogliosis in hippocampus of SNAP-25 mutant mouse (2006)
  • Author(s): 山森早織、勝又修、山科正平、朝倉哲也、佐藤拓、鈴木映二、渡辺滋、宮岡等、東貞宏、片岡正和、高橋正身
  • Organizer: 第49回日本神経化学会大会(第28回日本生物学的精神医学会、第36回日本神経精神薬理学会)
  • Place of Presentation: 名古屋
• [Presentation] SNAP-25変異ノックインマウス脳における神経伝達物質に関する研究 (2006)
  • Author(s): 鈴木映二、佐藤拓、朝倉哲也、山森早織、東貞宏、渡辺滋、横山正宗、宮岡等、片岡正和、高橋正身
  • Organizer: 第49回日本神経化学会大会(第28回日本生物学的精神医学会、第36回日本神経精神薬理学会)
  • Place of Presentation: 名古屋
• [Book] Encyclopedia of Neuroscience (2008)
  • Author(s): Takahashi, M.
  • Publisher: Synapse. In M. D. Binder, N. Hirokawa, U. Windhorst (Eds.)Heiderberg : Springer
• [Book] 神経伝達物質の放出を制御するシグナル (2008)
  • Author(s): 高橋正身、板倉誠
  • Publisher: 蛋白質核酸酵素
• [Book] アストロサイトにおける神経伝達物質の開口放出 (2007)
  • Author(s): 高橋正身、板倉誠、山森早織
  • Publisher: Brain and Nerve
• [Book] Encyclopedia of Neuroscience
  • Author(s): Takahashi, M.
  • Publisher: FM1-43. In M. D. Binder, N. Hirokawa, U. Windhorst (Eds.)Heiderberg : Springer