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

2008 Fiscal Year Final Research Report

• 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
• 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

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] 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
• [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] 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] 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] 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
• [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
  • Year and Date: 20080401-06
• [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
  • Year and Date: 20071104-07
• [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
  • Year and Date: 20070218-19
• [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
  • Year and Date: 20060719-21
• [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
  • Year and Date: 20051209-10
• [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
  • Year and Date: 20051003-04
• [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
  • Year and Date: 20050519-20
• [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] 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
  • Year and Date: 20041025-30
• [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
  • Year and Date: 20040510-12
• [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.
  • Total Pages: 129-137
  • 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
  • Total Pages: 35-39
  • Publisher: 羊土社
• [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
  • Total Pages: 83-94
  • Publisher: 東京
• [Remarks]
  • URL: http://www.dent.kyushu-u.ac.jp/sosiki/a04/index.html