Studies on a novel signaling molecule, PRIP invo ived in GABAA receptor function

• Project/Area Number: 16109010
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Functional basic dentistry
• Research Institution: Kyushu University
• Principal Investigator: HIATA Masato Kyushu University, 大学院・歯学研究院, 教授 (60136471)
• Co-Investigator(Kenkyū-buntansha): KANEMATSU Takashi 広島大学, 大学院・医歯薬学総合研究科, 教授 (10264053) ; TAKEUCHI Hiroshi 九州大学, 大学院・歯学研究院, 助教 (70304813) ; MATSUDA Miho 九州大学, 大学院・歯学研究院, 助教 (40291520) ; KANG Youngnam 大阪大学, 大学院・歯学研究科, 教授 (50177755)
• Project Period (FY): 2004 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥113,490,000 (Direct Cost: ¥87,300,000、Indirect Cost: ¥26,190,000); Fiscal Year 2008: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000); Fiscal Year 2007: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000); Fiscal Year 2006: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000); Fiscal Year 2005: ¥26,910,000 (Direct Cost: ¥20,700,000、Indirect Cost: ¥6,210,000); Fiscal Year 2004: ¥40,170,000 (Direct Cost: ¥30,900,000、Indirect Cost: ¥9,270,000)
• Keywords: ABA_A受容体 / 咬合 / ノックアウトマウス / カルシウム / リン酸化 / 抗不安薬 / GABA(A)受容体 / PRIP / インスリン / Akt / CABA(A)受容体 / ノックアワトマウス / 脳機能 / 行動学的解析 / ベンゾジアゼピン系薬剤 / GABA_A受容体 / 三叉神経

Research Abstract

新しいタンパク質分子、PRIPを見いだした。この分子を持っていないマウス(変異マウス)を作製して多方面から解析した。脳の機能は興奮と抑制のバランスで保たれているが、変異マウスは抑制に関わるGABA_A受容体の機能と細胞膜への輸送に異常が認められ、PRIPはGABAへ受容体が適切な機能を発揮するためには必須の分子であることが分かった。一方、正しい咀噛が出来ないようなマウスでは脳内のPRIPの量に変化は認められなかったが、GABA_A受容体の機能と関連すると思われる情動に関する異常行動を示した。

Research Products

• [Journal Article] Binding of phospholipase C-related but catalytically inactive protein tophosphatidylinositol 4, 5-bisphosphate via the PH domain (2009)
  • Author(s): Gao, J., Takeuchi, H., Zhao, Z., Fujii, M., Kanematsu, T., Hirata, M
  • Journal Title: Cell. Signal. (印刷中)
  • Peer Reviewed
• [Journal Article] Celecoxib-induced degradation of T-cell factors-1 and -4 in human coloncancer cells (2008)
  • Author(s): Takahashi-Yanaga, F., Yoshihara, T., Jingushi, K., Miwa, Y., Morimoto, S., Hirata, M., Sasaguri, T
  • Journal Title: Biochem. Biophys. Res. Commun 377 Pages: 1185-1190
  • Peer Reviewed
• [Journal Article] Differential columnar processing in local circuits of barrel and insular cortices (2008)
  • Author(s): Sato, H., Shimaniki, Y., Saito, M., Toyoda, H., Maeda, Y., Nokubi, T., Yamamoto, T., Kang, Y.
  • Journal Title: J. Neurosci. 28 Pages: 3076-3089
  • Peer Reviewed
• [Journal Article] Phospholipase Crelated inactive protein is implicated in the constitutive internalization of GABA_A receptors mediated by clathrin and AP2 adaptor complex (2007)
  • Author(s): Kanematsu, T., Fujii, M., Mizokami, A., Kittler, J.T., Nabekura. J., Moss, S.J. and Hirata, M.
  • Journal Title: J. Neurochem 101 Pages: 898-905
• [Journal Article] Changes in KCC2 phosphorylation in response to neuronal stress results in functional downregulation (2007)
  • Author(s): Wake, H., Watanabe, M., Moorhouse, A.J., Kanematsu, T., Horibe, S., Matsukawa, N., Asai, K., Ojika, K., Hirata. M. and Nabekura, J.
  • Journal Title: J. Neurosci 27 Pages: 16421650-16421650
• [Journal Article] Phosholipase Crelated inactive protein is involved in trafficking of γ2 subunitcontaining GABA_A receptor to cell surface (2007)
  • Author(s): Mizokami, A., Kanematsu, T., Ishibashi, H., Yamaguchi, T., Tanida, I., Takenaka, K., Nakayama, K.I., Fukami, K., Takenawa, T., Kominami, E., Moss, S.J., Yamamoto, T., Nabekura, J. and Hirata, M.
  • Journal Title: J. Neurosci. 27 Pages: 1692-1701
• [Journal Article] Phosholipase C-related inactive protein is involved in trafficking of γ2 subunit-containine GABA_A receptor to cell surface (2007)
  • Author(s): Mizokami, A. 他
  • Journal Title: Journal of Neuroscience 27 Pages: 1692-1701
  • Peer Reviewed
• [Journal Article] Changes in KCC2 phosphorylation in response to neuronal stress results in functional downregulation (2007)
  • Author(s): Wake, H, 他
  • Journal Title: Journal of Neuroscience 27 Pages: 1642-1650
  • Peer Reviewed
• [Journal Article] Phospholipase C-related inactive protein is implicated in internalization of GABA_A receptors mediated by clathrin and AP2 adaptor complex (2007)
  • Author(s): Kanematsu, T, 他
  • Journal Title: Journal of Neurochemistry 101 Pages: 898-905
  • Peer Reviewed
• [Journal Article] Modulation of GABA_A receptor phosphorylation and membrane trafficking by phospholipase Crelated inactive protein/protein phosphatase 1 and 2A signaling complex underlying brainderived neurotrophic factordependent regulation of GABAergic inhibition (2006)
  • Author(s): Kanematsu, T., Yasunaga, A., Mizoguchi, Y., Kuratani, A., Kittler, J.T., Jovanovic, J.N., Takenaka, K., Nakayama, K.I., Fukami, K., Takenawa, T., Moss, S.J., Nabekura, J. and Hirata, M.
  • Journal Title: J. Biol. Chem. 281 Pages: 22180-22189
• [Journal Article] Lysosomal turnover of GABARAP-phospholipid phospholipid conjugate is activated during differentiation of C2C12 cells to myotubes without inactivation of the mTor kinasesignaling pathway (2006)
  • Author(s): Tanida, I., Wakabayashi, M., Kanematsu, T., Minemoto-Ikeguchi, N., Sou, Y.-S., Hirata, M., Ueno, T. and Kominami, E.
  • Journal Title: Autophagy 2 Pages: 264-271
• [Journal Article] Protein phosphatase regulation by PRIP, a PLCrelated catalytically inactive protein Implications in the phosphomodulation of the GABA_A receptor- (2006)
  • Author(s): Yanagihori, S., Terunuma, M., Koyano, K., Kanematsuo, T., Ryu S.H. and Hirata, M.
  • Journal Title: Adv. Enz. Regul 46 Pages: 203-222
• [Journal Article] Ca^<2+>dependent regulation of calcitonin gene expression by the transcriptional repressor DREAM (2006)
  • Author(s): Matsuda, M., Yamamoto, T. and Hirata, M.
  • Journal Title: Endocrinology 147 Pages: 4608-4617
• [Journal Article] Characterization of the human PRIP-1 gene structure and transcriptional regulation (2006)
  • Author(s): Murakami, A., Matsuda, M., Nakasima, A. and Hirata, M.
  • Journal Title: Gene 382 Pages: 129-139
• [Journal Article] Modulation of GABA receptor phosphorylation and membrane trafficking by phospholipase C-related inactive protein/protein phosphatase 1 and 2A signaling complex underlying brain-derived neurotrophic factor-dependent regulation of GABAergic inhibition (2006)
  • Author(s): Kanematsu, T, et al.
  • Journal Title: J. Biol. Chem. 281 Pages: 22180-22189
• [Journal Article] Protein phosphatase regulation by PRIP, a PLC-related catalytically inactive protein -Implications in the phospho-modulation of the GABA_A receptor- (2006)
  • Author(s): Yanagihori, S., et al.
  • Journal Title: Adv. Enz. Regul. 46 Pages: 203-222
• [Journal Article] Ca^2+-dependent regulation of calcitonin gene expression by the transcriptional repressor DREAM (2006)
  • Author(s): Matsuda, M., et al.
  • Journal Title: Endocrinology 147 Pages: 4608-4617
• [Journal Article] Characterization of the human PRIP-1 gene structure and transcriptional regulation (2006)
  • Author(s): Murakami, A., et al.
  • Journal Title: Gene 382 Pages: 129-139
• [Journal Article] Involvement of GSK-3β and DYRK1B in differentiation-inducing factor-3-induced phosphorylation of cyclin D1 in HeLa cells (2006)
  • Author(s): Takahashi-Yanaga, F., et al.
  • Journal Title: J. Biol. Chem. 281 Pages: 38489-38497
• [Journal Article] Differentiation-inducing factor-1 alters canonical Wnt signaling and suppresses alkaline phosphatase expression in osteoblast-like cell lines (2006)
  • Author(s): Matsuzaki, E., et al.
  • Journal Title: J. Bone Miner. Res. 21 Pages: 1307-1316
• [Journal Article] Protein phosphatase regulation by PRIP, a PLC-related catalytically inactive protein-Implications in the phospho-modulation of the GABA_A receptor (2006)
  • Author(s): Yanagihori, S. et al.
  • Journal Title: Adv.Enz.Regul. (In press)
• [Journal Article] Role of PRIP-1, a novel Ins(1, 4, 5)P_3 binding protein, in Ins(1, 4, 5)P_3-mediated Ca^<2+> signaling (2005)
  • Author(s): Harada, K., Takeuchi, H., Oike, M., Matsuda, M., Kanematsu, T., Yagisawa, H., Nakayama, K.I., Maeda, K., Erneux, C. and Hirata, M.
  • Journal Title: J. Cell. Physiol 202 Pages: 422-433
• [Journal Article] Solution structure of microtubule associated protein light chain 3 and identification of its functional subdomains (2005)
  • Author(s): Kouno, T., Mizuguchi, M., Tanida, I., Ueno, T., Kanematsu, T., Mori, Y., Shinoda, H., Hirata, M., Kominami, E. and Kawano, K.
  • Journal Title: J. Biol. Chem. 280 Pages: 24610-24617
• [Journal Article] Phosphatidylinositol 4-phosphate-5-kinase regulates fission yeast cell integrity through a phospholipase Cmediated protein kinase C-independent pathway (2005)
  • Author(s): Deng, L., Sugiura, R., Ohta, K., Tada, K., Suzuki, M., Hirata, M., Nakamura, S., Shuntoh, H. and Kuno, T.
  • Journal Title: J. Biol. Chem. 280 Pages: 27561-27568
• [Journal Article] Direct interaction of N-ethylmaleimide-sensitive factor with GABA_A receptor β subunits (2005)
  • Author(s): Goto, H., Terunuma, M., Kanematsu, T., Misumi, Y., Moss, S.J. and Hirata. M.
  • Journal Title: Mol. Cell. Neurosc 30 Pages: 197-206
• [Journal Article] Role of PRIP-1,a novel Ins(1,4,5)P_3 binding protein, in Ins(1,4,5)P_3-mediated Ca^<2+> signaling (2005)
  • Author(s): Harada, K. et al.
  • Journal Title: J.Cell.Physiol. 202 Pages: 422-433
• [Journal Article] Solution structure of microtubule-associated protein light chain 3 and identification of its functional subdomains (2005)
  • Author(s): Koune, T. et al.
  • Journal Title: J.Biol.Chem. 280 Pages: 24610-24617
• [Journal Article] Phosphatidylinositol-4-phosphate-5-kinase regulates fission yeast cell integrity through a phospholipase C-mediated proteinkinase C-independent pathway (2005)
  • Author(s): Deng, L. et al.
  • Journal Title: J.Biol.Chem. 280 Pages: 27561-27568
• [Journal Article] Direct interaction of N-ethylmaleimide-sensitive factor with GABA_A receptor β-subunits (2005)
  • Author(s): Goto, H. et al.
  • Journal Title: Mol.Cell.Neurosci. 30 Pages: 197-206
• [Journal Article] Differentiation-inducing factor-1 induces cyclin D1 degradation through the phosphorylation of Thr286 in squamous cell carcinoma (2005)
  • Author(s): Mori, J. et al.
  • Journal Title: Exp.Cell Res. 310 Pages: 426-433
• [Journal Article] D-6-Deoxy myoinositol 1,3,4,5-tetrakis phosphate, a mimic of Dmyoinositol 1,3,4,5tetrakisphosphate : biological activity and pHdependent conformational properties (2004)
  • Author(s): Home, G., Maechling, C., Fleig, A., Hirata, M., Penner, R., Spiess, B. and Potter, B.V.L.
  • Journal Title: Biochem. Biophys. Res. Commun. 320 Pages: 1262-1270
• [Journal Article] GABA_A receptor phosphodependent modulation is regulated by phospholipase Crelated inactive protein type 1, a novel protein phosphatase 1 anchoring protein (2004)
  • Author(s): Terunuma, M., Jang, I-S., Ha, S.H., Kittler, J.T., Kanematsu, T., Jovanovic, J.N., Nakayama, K.I., Akaike, N., Ryu, S.H., Moss, S.J. and Hirata, M.
  • Journal Title: J. Neurosci 24 Pages: 7074-7084
• [Journal Article] Hypersensitivity to pentylenetetrazoleinduced convulsion in mice lacking the PLCrelated inactive protein-1 (2004)
  • Author(s): Yamaguchi, T., Kubota, T., Kanematsu, T., Nakayama K.I., Hirata, M. and Yamamoto, T.
  • Journal Title: Brain Res. 1025 Pages: 237-240
• [Journal Article] GABA_A receptor phospho-dependent modulation is regulated by phospholipase C-related inactive protein type 1,a novel protein phosphatase 1 anchoring protein (2004)
  • Author(s): Terunuma, M. et al.
  • Journal Title: J.Neurosci. 24 Pages: 7074-7084
• [Journal Article] Hypersensitivity to pentylenetetrazole-induced convulsion in mice lacking the PLC-related inactive protein-1 (2004)
  • Author(s): Yamaguchi, T. et al.
  • Journal Title: Brain Res. 1025 Pages: 237-240
• [Journal Article] D-6-Deoxy myo-inositol 1,3,4,5-tetrakisphosphate, a mimic of D-myo-inositol 1,3,4,5-tetrakisphosphate : biological activity and pH-dependent conformational properties (2004)
  • Author(s): Horne, G. et al.
  • Journal Title: Biochem.Biophys.Res.Commun. 320 Pages: 1262-1270
• [Journal Article] Glycogen synthase kinase-3beta is tyrosine-phosphorylated by MEK 1 in human skin fibroblasts (2004)
  • Author(s): Takahashi-Yanaga, F. et al.
  • Journal Title: Biochem.Biophys.Res.Commun. 316 Pages: 411-415
• [Journal Article] Binding of 14-3-3β but not 14-3-3σ controls the cytoplasmic localization of CDC25B : binding site preference of 14-3-3 subtypes and the subcellular localization of CDC25B (2004)
  • Author(s): Uchida, S. et al.
  • Journal Title: J.Cell Sci. 117 Pages: 3011-3020
• [Journal Article] Nuclear export signal in CDC25B (2004)
  • Author(s): Uchida, S. et al.
  • Journal Title: Biochem.Biophys.Res.Commun. 316 Pages: 226-232
• [Presentation] Action of PRIP, an Ins(1, 4, 5)P_3 binding protein, in insulin secretion (2008)
  • Author(s): Kanematsu, T., Shioi, S., Kiyoshima, T., Sakai, H. and Hirata, M.
  • Organizer: Keystone Symposium Islet Biology, Snowmass, Utah
• [Presentation] Action of PRIP, an Ins(l, 4, 5)P_3 binding protein, in insulin secretion (2008)
  • Author(s): Kanematsu, T., Shioi, S., Kiyoshima, T., Sakai, H., Hirata, M.
  • Organizer: Keystone Symposium“Islet Biology"
  • Place of Presentation: Snowmass, Utah, USA
• [Presentation] Finding of a novel signaling molecule, PRIP and exploring its cellular functions-Involvement in neuroscience and beyond- (2007)
  • Author(s): Keystone Symposium Islet Biology, Snowmass, Utah
  • Organizer: The 2^<nd> International Symposium for Interface Oral Health Science in Sendai, February
  • Place of Presentation: Sendai
• [Presentation] Finding of a new Ins(1, 4, 5)P_3 binding protein, PRIP and exploring its cellular functions-Involvement in neuroscience and beyond- (2007)
  • Author(s): Hirata, M. and Kanematsu, T.
  • Organizer: Howard Hughes Medical Institute Janelia Farm Conference, Farm
  • Place of Presentation: Janelia Farm
• [Presentation] Finding of a new Ins(1,4,5)P_3 binding protein,PRIP and exploring its cellular functions -Involvement in neuroscience and beyond- (2007)
  • Author(s): Hirata, M.
  • Organizer: Howard Hughes Medical Institute Janelia Farm Conference
  • Place of Presentation: Janelia Farm, VA, USA
• [Presentation] Role of PRIP in trafficking of GABAA receptors (2006)
  • Author(s): Hirata, M., Kuratani, A. and Kanematsu, T.
  • Organizer: The 29^<th> Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Kyoto
• [Presentation] Finding new proteins and dissecting its functions (2005)
  • Author(s): Hirata, M.
  • Organizer: Lecture in Pohang Unversity of Science and Technology
  • Year and Date: 2005-05-18
• [Presentation] PRIP, a new Ins(1,4,5)P_3 binding protein, its extension to neuroscience and more (2005)
  • Author(s): Hirata. M. and Kanematsu, T.
  • Organizer: 62^<nd> KSBMB Annual Meeting in 2005
• [Presentation] Protein phosphatase regulation by PRIP, PLCrelated catalytically inactive protein : Significance in functional modulation of GABA_A receptors (2005)
  • Author(s): Hirata, M., Yanagihori, S., Terunuma, M. and Kanematsu, T.
  • Organizer: The 46^<th> International Symposium on "Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues
• [Presentation] Phospholipase Crelated inactive protein/protein phosphatase signaling complex regulates BDNFmodulated GABA_A receptor phosphorylation and membrane trafficking (2005)
  • Author(s): Kanematsu, T. and Hirata, M.
  • Organizer: The 4th Neuroscience Workshop in Kyushu
  • Place of Presentation: Hisayama
• [Presentation] PRIP, a molecule involved in Ins(1, 4, 5)P_3/Ca^<2+>and GABA signaling (2004)
  • Author(s): Hirata, M.
  • Organizer: The 3rd Japanese Biochemical Society Biofrontier Symposium New Aspect of Phospholipid Biology 2004"
  • Place of Presentation: Kamakura Prince Hotel
• [Presentation] Apoptosis of tumor cells caused by IP6 (2004)
  • Author(s): Hirata, M., Matsuda, M., Sandra, F. and Matsuki, N.
  • Organizer: The 7^<th> International Conference on Anticancer Research
  • Place of Presentation: Corfu, Greece
• [Book] 新奇分子を介したGABA_A受容体輸送調節の分子基盤解明「ブレインサイエンス・レビュー2008」 (2009)
  • Author(s): 兼松 隆
  • Publisher: クバプロ(印刷中)
• [Book] Involvement of PRIP, a new signaling molecule, in neuroscience and beyond oral health science.In "Interface Oral Health Science 2007"(Watanabe, M. and Okuno, O.eds) (2007)
  • Author(s): Hirata, M., Kanematsu, T. and Mizokami, A.
  • Publisher: (Springer, Tokyo)
• [Book] ファーウエスタン法分子間相互作用解析ハンドブック(磯辺俊明、中山敬一、伊藤隆司編) (2007)
  • Author(s): 兼塗隆、藤井誠、平田雅人
  • Publisher: 羊土社
• [Book] Interface Oral Health Science 2007 (2007)
  • Author(s): Hirata, M., Kanematsu, T.and Mizokami, A.
  • Total Pages: 385
  • Publisher: Springer,Tokyo
• [Book] GABA受容体機能に関わる新しい分子「ブレインサエンス・レビュー2004」(伊藤正男・川合述史編) (2004)
  • Author(s): 平田雅人、韮竺隆、照沼美穂
  • Publisher: 東京
• [Remarks]
  • URL: http://www.dent.kyushu-u.ac.jp/sosiki/a04/index.html
• [Remarks]
  • URL: http://www.dent.kyushu-u.ac.jp/sosiki/a04/index.html
• [Remarks]
  • URL: http://www.dent.kyushu-u.ac.jp/sosiki/aO4/index.html