Possible involvement of a new molecule, PRIP in exocytosis

2011 Fiscal Year Final Research Report

• Project/Area Number: 21249089
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Kyushu University
• Principal Investigator: HIRATA Masato 九州大学, 歯学研究院, 教授 (60136471)
• Co-Investigator(Kenkyū-buntansha): TAKEUCHI Hiroshi 九州大学, 大学院・歯学研究院, 准教授 (70304813) ; MATSUDA Miho 九州大学, 大学院・歯学研究院, 助教 (40291520)
• Project Period (FY): 2009 – 2011
• Keywords: 開口分泌 / SNARE / 膜リン脂質 / PHドメイン / C2ドメイン / リン酸化

Research Abstract

We have isolated a novel protein, PRIP(PLC-related but catalytically inactive protein), followed by generation of the gene-deficient mice(KO mice). KO mice exhibited up-regulation of gonadotropins and insulin, indicating that PRIP might be involved in events common to vesicular fusion processes. In the current studies, therefore, we have explored the mechanisms by which PRIP is involved in exocytosis. The results suggest that PRIP is negatively involved in the dense-core vesicle secretion of PC12 cells, by occupying the membrane phospholipids required for the secretion with the PH domain, and interfering SNARE proteins by the C2 domains. Furthermore, PRIP is involved in the phospho-modulation of exocytosis by regulating activities of protein phosphatases.

Research Products

• [Journal Article] Phospholipase C-related but catalytically inactive protein(PRIP) modulates synaptosomal-associated protein 25(SNAP-25) phosphorylation and exocytosis (2012)
  • Author(s): Gao, J., Takeuchi, H., Zhang, Z., Fukuda, M. and Hirata, M.
  • Journal Title: J. Biol. Chem Volume: 287 Pages: 10565-10578
• [Journal Article] Second basic pockets contribute to the localization of PX domains by binding to phosphatidic acid (2012)
  • Author(s): Takeuchi, H., Zhang, Z., Gao, J., Sugiyama, G., Takeuchi, T., and Hirata, M.
  • Journal Title: Adv. Enz. Regul Volume: 52 Pages: 183-194
• [Journal Article] DIF-1 inhibits the Wnt/υ-catenin signaling pathway by inhibiting TCF7L2 expression in colon cancer cell lines (2012)
  • Author(s): Jingushi, K., Takahashi-Yanaga, F., Yoshihara, T., Shiraishi, F., Watanabe, Y., Hirata, M., Morimoto, S., and Sasaguri, T.
  • Journal Title: Biochem. Pharmacol Volume: 83 Pages: 47-56
• [Journal Article] Dysfunction of extrasynaptic GABAergic transmission in PRIP-1 KO mice is associated with an epilepsy phenotype (2012)
  • Author(s): Zhu, G., Yoshida, S., Migita, K., Yamada, J., Mori, F., Tomiyama, M., Wakabayashi, K., Kanematsu, T., Hirata, M., Kaneko, S., Ueno, S., and Okada, M.
  • Journal Title: J. Pharmacol. Exp. Ther Volume: 340 Pages: 520-528
• [Journal Article] Involvement of PRIP, phospholipase C-related but catalytically inactive protein, in bone formation (2011)
  • Author(s): Tsutsumi, K., Matsuda, M., Kotani, M., Mizokami, A., Murakami, A., Takahashi, I., Terada, Y., Kanematsu, T., Fukami, K., Takenawa, T., Jimi, E. and Hirata, M.
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 31032-31042
• [Journal Article] Phenotypes of pain behavior in phospholipase C-related but catalytically inactive protein type 1 knockout mice (2011)
  • Author(s): Migita, K., Tomiyama, M., Yamada, J., Fukuzawa, M., Kanematsu, T., Hirata, M., and Ueno, S.
  • Journal Title: Mol. Pain Volume: 7 Pages: 79
• [Journal Article] Dual signaling pathways of arterial constriction by extracellular UTP in the rat (2011)
  • Author(s): Sugihara, M., Morita, H., Matsuda, M., Umebayashi, H., Kajioka, S., Ito, S., Nishida, M., Inoue, Ryosuke., Futatsuki, T., Yamazaki, J., Mori, Y., Inoue, Ryuji., Ito, Y., Abe, K. and Hirata, M.
  • Journal Title: J. Pharmacol. Sci Volume: 115 Pages: 293-305
• [Journal Article] Characterization of PXK as a protein involved in epidermal growth factor receptor trafficking (2010)
  • Author(s): Takeuchi, H., Takeuchi, T., Gao, J., Cantley, L. C. and Hirata, M.
  • Journal Title: Mol. Cell. Biol Volume: 30 Pages: 1689-1702
• [Journal Article] Phospholipase C-related but catalytically inactive protein is required for insulininduced cell surface expression of・-aminobutyric acid type A receptors (2010)
  • Author(s): Fujii, M., Kanematsu, T., Ishibashi, H., Fukami, K., Takenawa, T., Nakayama, K. I., Moss, S. J., Nabekura, J., Hirata, M.
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 4837-4846
• [Journal Article] GABAA receptor subunit alteration-dependent diazepam insensitivity in the cerebellum of phospholipase C-related inactive protein knockout mice (2010)
  • Author(s): Mizokami, A., Tanaka, H., Ishibashi, H., Umebayashi, H., Fukami, K., Takenawa, T., Nakayama, K. I., Yokoyama, T., Nabekura, J., Kanematsu, T. and Hirata, M.
  • Journal Title: J. Neurochem Volume: 114 Pages: 302-310
• [Journal Article] Genetic reduction of GABAA receptorγ2 subunit expression potentiates the immobilizing action of isoflurane (2010)
  • Author(s): Seo, K., Seino, H., Yoshikawa, H., Petrenko, A. B., Baba, H., Fujiwara, N., Someya, G., Kawano, Y., Maeda, T., Matsuda, M., Kanematsu, T. and Hirata, M.
  • Journal Title: Neurosci. Lett Volume: 472 Pages: 1-4
• [Journal Article] Dictyostelium differentiation-inducing factor-1 binds to mitochondrial malate dehydrogenase and inhibits its activity (2010)
  • Author(s): Matsuda, T., Takahashi-Yanaga, F., Yoshihara, T., Maenaka, K., Watanabe, Y., Miwa, Y., Morimoto, S., Kubohara, Y., Hirata, M. and Sasaguri, T.
  • Journal Title: J. Pharmacol. Sci Volume: 112 Pages: 320-326
• [Journal Article] Assay of dense-core vesicle exocytosis using permeabilized PC12 cells (2010)
  • Author(s): Gao, J., Takeuchi, H., Umebayashi, H., Zhang, Z., Matsuda, M. and Hirata, M.
  • Journal Title: Adv. Enz. Regul Volume: 50 Pages: 237-246
• [Journal Article] Orofacial movements in phospholipase C-related catalytically inactive protein-1/2 double knockout mice : Effect of the GABAergic agent diazepam and the D1 dopamine receptor agonist SKF 83959 (2010)
  • Author(s): Tomiyama, T., Song, L., Kobayashi, M., Kinsella, A., Kanematsu, T., Hirata, M., Koshikawa, N. and Waddington, J. L.
  • Journal Title: Synapse Volume: 64 Pages: 714-720
• [Journal Article] Anti-angiogenic effects of differentiation-inducing factor-1 involving VEGFR-2 expression inhibition independent of the Wnt/β-catenin signaling pathway (2010)
  • Author(s): Yoshihara, T., Takahashi-Yanaga, F., Shiraishi, F., Morimoto, S., Watanabe, Y., Hirata, M., Hoka, S. and Sasaguri, T.
  • Journal Title: Mol. Cancer Volume: 9 Pages: 245
• [Journal Article] Surface Expression of GABAA Receptors. Roles for the Binding Protein- (2010)
  • Author(s): Kanematsu, T., Fujii, M., Tanaka, H., Umebayashi, H. and Hirata, M.
  • Journal Title: J. Oral Biosci Volume: 52 Pages: 322-329
• [Journal Article] Binding of phospholipase C-related but catalytically inactive protein to phosphatidylinositol 4, 5-bisphosphate via the PH domain (2009)
  • Author(s): Gao, J., Takeuchi, H., Zhao, Z., Fujii, M., Kanematsu, T. and Hirata, M.
  • Journal Title: Cell. Signal Volume: 21 Pages: 1180-1186
• [Journal Article] Involvement of phospholipase C-related inactive protein in the mouse reproductive system through the regulation of gonadotropin levels (2009)
  • Author(s): Matsuda, M., Tsutsumi, K., Kanematsu, T., Fukami, K., Terada, Y., Takenawa, T., Nakayama, K. I. and Hirata, M.
  • Journal Title: Biol. Reprod Volume: 81 Pages: 681-689
• [Presentation] Phosphoregulation of exocytosis by PRIP (2011)
  • Author(s): Takeuchi, H., Gao, J., Zhang, Z., Sugiyama, G., Nagano, K., and Hirata, M.
  • Organizer: The 10^<th> JBS Biofrontier Symposium International Symposium on New Aspects of Phospholipid Biology and Medicine 2011(The 100^<th> Anniversary of Kyushu University)
  • Place of Presentation: Fukuoka
  • Year and Date: 20111114-16
• [Presentation] Involvement of PRIP in bone formation (2011)
  • Author(s): Hirata, M., Tsutsumi, K., Kotani, M., Mizokami, A., and Matsuda M
  • Organizer: The 52^<nd> International Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues
  • Place of Presentation: Bologna
  • Year and Date: 20110926-27
• [Presentation] リン酸化制御による開口分泌の修飾(シンポジウム) (2011)
  • Author(s): 竹内弘、高靖、張〓、杉山悟郎、平田雅人
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 20110322-24
• [Presentation] PRIPの骨代謝における機能(教育講演) (2011)
  • Author(s): 平田雅人
  • Organizer: 第9回歯科骨粗鬆症研究会学術大会小倉リーセントホテル
  • Place of Presentation: 北九州市
  • Year and Date: 2011-03-13
• [Presentation] PRIP, a new Ins(1, 4, 5) P_3 binding protein, its extension to neuroscience and beyond (2010)
  • Author(s): Hirata, M., Gao, J., Matsuda, M., Takeuchi, H., and Kanematsu, T.
  • Organizer: The 2^<nd> Pohang Conference on Cellular Signaling
  • Place of Presentation: Pohang, Korea
  • Year and Date: 20100202-03
• [Presentation] Inhibition of exocytosis by PRIP, PLC-related but catalytically inactive protein (2010)
  • Author(s): Hirata, M.
  • Organizer: International Symposium 2010, Cutting-edge Biomedical Research
  • Place of Presentation: Pusan, Korea
  • Year and Date: 2010-02-03
• [Presentation] 新規タンパク質の機能解明に向けた奮闘 (2010)
  • Author(s): 横浜市
  • Organizer: 第22回蔵王カンファレンス
  • Place of Presentation: 蔵王温泉
  • Year and Date: 2010-01-29
• [Presentation] Inhibition of exocytosis by PRIP, phospholipase C-related inactive protein (2009)
  • Author(s): Hirata, M., Gao, J. and Takeuchi, H.
  • Organizer: The 50^<th> International Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues
  • Place of Presentation: Bologna
  • Year and Date: 20090928-29
• [Presentation] GABAA受容体の輸送に関わるメカニズム (2009)
  • Author(s): 兼松隆、平田雅人
  • Organizer: 第82回日本薬理学会年会シンポジウム
  • Place of Presentation: 横浜市
  • Year and Date: 20090316-18
• [Presentation] Inhibitory role of PRIP in dense core vesicle exocytosis (2009)
  • Author(s): Takeuchi, H., Gao, J., Zhang, Z., Hirata, M.
  • Organizer: 21^<st> IUBMB and 12^<th> FAOBMB International Congress of Biochemistry and Molecular Biology
  • Place of Presentation: Shanghai, China, August
  • Year and Date: 2009-02-07
• [Remarks]
  • URL: http://www.mcb.dent.kyushu-u.ac.jp/