Molecular mechanisms for neurogenesis and psychiatric dysfunction in postnatal and adult periods

• Project/Area Number: 21689013
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Nagoya University
• Principal Investigator: ENOMOTO Atsushi 名古屋大学, 大学院・医学系研究科, 特任准教授 (20432255)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥26,910,000 (Direct Cost: ¥20,700,000、Indirect Cost: ¥6,210,000); Fiscal Year 2011: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000); Fiscal Year 2010: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000); Fiscal Year 2009: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
• Keywords: 分子 / 発生医学 / Girdin / DISCI / 神経新生 / 海馬 / 統合失調症 / DISC1

Research Abstract

We showed that the actin-binding protein Girdin binds to DISC1, a susceptibility gene for schizophrenia, and regulates the migration and positioning of newborn neurons in the dentate gyrus of the hippocampus during postnatal and adult periods. Furthermore, we identified that Girdin is crucial for the migration of neuroblasts born in the subventricular zone. We also studied the function of two members of the Girdin family of proteins, Gipie and Daple, and found that they regulate the ER stress response and the Wnt signaling pathway, respectively.

Research Products

• [Journal Article] Behavioral alterations associated withtargeted disruption of exons 2 and 3 ofthe Disc1 gene in the mouse (2011)
  • Author(s): Kuroda K, Yamada S, Tanaka M, IizukaM, Yano H, Mori D, Tsuboi D, NishiokaT, Namba T, Iizuka Y, Kubota S, Nagai T, Ibi D, Wang R, Enomoto A, Isotani-Sakakibara M, Asai N, Kimura K, Kiyonari H, Abe T, Mizoguchi A, Sokabe M, Takahashi M, Yamada K, Kaibuchi K
  • Journal Title: Hum Mol Genet. Volume: 20 Pages: 4666-4683
  • Peer Reviewed
• [Journal Article] Girdin is an intrinsic regulator of neuroblast chain migration in the rostral migratory stream of the postnatal brain (2011)
  • Author(s): Wang Y, Kaneko N, Asai N, Enomoto A, Isotani-Sakakibara M, Kato T, Asai M, Murakumo Y, Ota H, Hikita T, Namba T, KurodaK, Kaibuchi K, Ming GL, SongH, Sawamoto K, Takahashi M.
  • Journal Title: J Neurosci. Volume: 31 Pages: 8109-8122
  • Peer Reviewed
• [Journal Article] NMDA receptor regulates migration of newly generated neurons in the adult hippocampus via Disrupted-In-Schizophrenia 1(DISC1). (2011)
  • Author(s): Namba T, Ming GL, Song H, Waga C, Enomoto A, Kaibuchi K, Kohsaka S, Uchino S.
  • Journal Title: J Neurochem. Volume: 18 Pages: 34-44
  • Peer Reviewed
• [Journal Article] The actin-binding protein Girdin and its Akt-mediated phosphorylation regulate neointima formation after vascular injury (2011)
  • Author(s): Miyake H, Maeda K, Asai N, Shibata R, Ichimiya H, Isotani-Sakakibara M, Yamamura Y, Kato K, Enomoto A, Takahashi M, Murohara T.
  • Journal Title: Circ Res. Volume: 108 Pages: 1170-1179
  • Peer Reviewed
• [Journal Article] Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cells (2011)
  • Author(s): Matsushita, E., Asai, N., Enomoto, A., Kawamoto, Y., Kato, T., Mii, S., Maeda, K., Shibata, R., Hattori, S., Hagikura, M., Takahashi, K., Sokabe, M., Murakumo, Y., Murohara, T., and Takahashi, M.
  • Journal Title: Mol. Biol. Cell Volume: 22 Pages: 736-747
  • Peer Reviewed
• [Journal Article] Analysis of GDNF-inducible zinc finger protein 1expression in human diseased kidney (2011)
  • Author(s): Saito, S., Murakumo, Y., Tsuzuki, T., Dambara, A., Kato, T., Enomoto, A., Asai, N., Maruyama, S., Matsuo, S., and Takahashi, M.
  • Journal Title: Human Pathol. Volume: 42 Pages: 848-858
  • Peer Reviewed
• [Journal Article] Loss of Sprouty2 partially rescues renal hypoplasia and stomach hypoganglionosis but not intestinal aganglionosis in Ret Y1062F mutant mice (2011)
  • Author(s): Miyamoto R, Jijiwa M, Asai M, Kawai K, Ishida-Takagishi M, Mii S, Asai N, Enomoto A, Murakumo Y, Yoshimura A, Takahashi M.
  • Journal Title: Dev Biol. Volume: 349 Pages: 160-168
  • Peer Reviewed
• [Journal Article] Behavioral alterations associated with targeted disruption of exons 2 and 3 of the Disci gene in the mouse (2011)
  • Author(s): Kuroda K, et al(計25名)
  • Journal Title: Hum Mol Genet Volume: 20 Pages: 4666-4683
  • Peer Reviewed
• [Journal Article] NMDA receptor regulates migration of newly generated neurons in the adult hippocampus via Disrupted-In-Schizophrenia 1 (DISC1) (2011)
  • Author(s): Namba T, et al(計8名)
  • Journal Title: J Neurochem Volume: 18 Issue: 1 Pages: 34-44
  • DOI: 10.1111/j.1471-4159.2011.07282.x
  • Peer Reviewed
• [Journal Article] Girdin is an intrinsic regulator of neuroblast chain migration in the rostral migratory stream of the postnatal brain (2011)
  • Author(s): Wang Y, et al(計17名)
  • Journal Title: J Neurosci Volume: 31 Pages: 8109-8122
  • Peer Reviewed
• [Journal Article] Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cells (2011)
  • Author(s): Etsushi Matsushita
  • Journal Title: Molecular Biology of the Cell Volume: 22 Pages: 736-747
  • Peer Reviewed
• [Journal Article] Loss of Sprouty2 partially rescues renal hypoplasia and stomach hypoganglionosis but not intestinal aganglionosis in Ret Y1062F mutant mice (2011)
  • Author(s): Rieko Miyamoto
  • Journal Title: Developmental Biology Volume: 349 Pages: 160-168
  • Peer Reviewed
• [Journal Article] Analysis of DOK-6function in downstream signaling of RET in human neuroblastoma cells (2010)
  • Author(s): Kurotsuchi A, Murakumo Y, Jijiwa M, Kurokawa K, Itoh Y, Kodama Y, Kato T, Enomoto A, Asai N, Terasaki H, Takahashi M.
  • Journal Title: Cancer Sci. Volume: 101 Pages: 1147-1155
  • NAID: 10026592015
  • Peer Reviewed
• [Journal Article] Analysis of DOK-6 function in downstream signaling of RET in human neuroblastoma cells (2010)
  • Author(s): Ai Kurotsuchi
  • Journal Title: Cancer Science Volume: 101 Pages: 1147-1155
  • Peer Reviewed
• [Journal Article] Roles of disrupted-in-schizophrenia 1-interactingprotein girdin in postnatal development of the dentate gyrus (2009)
  • Author(s): Enomoto A, Asai N, Namba T, Wang Y, Kato T, Tanaka M, Tatsumi H, Taya S, Tsuboi D, Kuroda K, Kaneko N, Sawamoto K, Miyamoto R, Jijiwa M, Murakumo Y, Sokabe M, Seki T, Kaibuchi K, Takahashi M.
  • Journal Title: Neuron Volume: 63 Pages: 774-787
  • Peer Reviewed
• [Journal Article] Expression of Ret finger protein correlates with outcomes in endometrial cancer (2009)
  • Author(s): Tsukamoto H, Kato T, Enomoto A, Nakamura N, Shimono Y, Jijiwa M, Asai N, Murakumo Y, Shibata K, Kikkawa F, Takahashi M.
  • Journal Title: Cancer Sci. Volume: 100 Pages: 1895-1901
  • NAID: 10027195768
  • Peer Reviewed
• [Journal Article] A novel Drosophila Girdin-like protein is involved in Akt pathway control of cell size (2009)
  • Author(s): Puseenam A, Yoshioka Y, Nagai R, Hashimoto R, Suyari O, Itoh M, Enomoto A, Takahashi M, Yamaguchi M.
  • Journal Title: Exp. Cell Res. Volume: 315 Pages: 3370-3380
  • Peer Reviewed
• [Journal Article] Characterization of theHDAC1 complex that regulates the sensitivity of cancer cells to oxidative stress (2009)
  • Author(s): Kato T, Shimono Y, Hasegawa M, Jijiwa M, Enomoto A, Asai N, Murakumo Y, Takahashi M.
  • Journal Title: Cancer Res. Volume: 69 Pages: 3597-3604
  • Peer Reviewed
• [Journal Article] Roles of disrupted-in-schizophrenia 1-interacting protein girdin in postnatal development of the dentate gyrus. (2009)
  • Author(s): Atsushi Enomoto
  • Journal Title: Neuron 63 Pages: 774-787
  • Peer Reviewed
• [Journal Article] Characterization of the HDAC1 complex that regulates the sensitivitv of cancer Cells to oxidative stress. (2009)
  • Author(s): Takuya Kato
  • Journal Title: Cancer Research 69 Pages: 3597-3604
  • Peer Reviewed
• [Journal Article] Cell biology of the movement of breast cancer cells : intracellular signalling and the actin cytoskeleton. (2009)
  • Author(s): Ping Jiang
  • Journal Title: Cancer Letters 284 Pages: 122-130
  • Peer Reviewed
• [Presentation] Cell-cell contact dependent regulatory role of RFP in integrin beta1 expression (2011)
  • Author(s): Kato, T., Enomoto, A., Weng, L., Asai, M., Murakumo, Y., Takahashi, M.
  • Organizer: The American Society of Cell Biology 2011 Annual Meeting
  • Place of Presentation: Denver
  • Year and Date: 2011-12-13
• [Presentation] Cell-cell contact dependent regulatory role of RFP in integrin beta1 expression (2011)
  • Author(s): Kato, T., Enomoto, A., Weng, L., Asai, M., Murakumo, Y., Takahashi, M.
  • Organizer: The American Society of Cell Biology, 2011 Annual Meeting
  • Place of Presentation: デンバー(米国)
  • Year and Date: 2011-12-13
• [Presentation] Girdin/GIV's partner Rabenosyn-5controls turnover of Akt (2011)
  • Author(s): Weng, L., Enomoto, A., Takahashi, M.
  • Organizer: The American Society of Cell Biology 2011 Annual Meeting
  • Place of Presentation: Denver
  • Year and Date: 2011-12-12
• [Presentation] Girdin/GIV's partner Rabenosyn-5 controls turnover of Akt (2011)
  • Author(s): Weng, L., Enomoto, A., Takahashi, M.
  • Organizer: The American Society of Cell Biology, 2011 Annual Meeting
  • Place of Presentation: デンバー(米国)
  • Year and Date: 2011-12-12
• [Presentation] Analysis of DISC1 using knockout mice and new antibodies (2010)
  • Author(s): Kuroda, K., Mori, D., Namba, T., Tsuboi, D., Yano, H., Ibi, D., Tanaka, M., Isotani, M., Enomoto, A., Yamada, K., Sokabe, M., Takahashi M., Kaibuchi, K.
  • Organizer: Neuroscience 2010, SfN's 40th annual meeting
  • Place of Presentation: San Diego
  • Year and Date: 2010-11-15
• [Presentation] Analysis of DISC1 using knockout mice and new antibodies. (2010)
  • Author(s): Keisuke Kuroda
  • Organizer: Neuroscience 2010, SfN's 40th annual meeting
  • Place of Presentation: 米国サンディエゴ
  • Year and Date: 2010-11-15
• [Presentation] The Dvl-associatingprotein Daple regulates the activation of Rac and the remodeling of actincytoskeleton (2009)
  • Author(s): Takagishi, M., Enomoto, A., Kikuchi, A., Takahashi, M.
  • Organizer: The American Society of Cell Biology 49th Annual Meeting
  • Place of Presentation: San Diego
  • Year and Date: 2009-12-07
• [Presentation] The Dvl-associating protein Daple regulates the activation of Rac and the remodeling of actin cvtoskeleton. (2009)
  • Author(s): Maki Takagishi
  • Organizer: The American Society of Cell Biology, 49th Annual Meeting
  • Place of Presentation: サンディエゴ
  • Year and Date: 2009-12-07
• [Presentation] Roles of Disrupted-In-Schizophrenia 1-interactingprotein Girdin in postnatal development of the dentate gyrus (2009)
  • Author(s): Enomoto, A.
  • Organizer: Global COE Program the second international symposium
  • Place of Presentation: Nagoya
  • Year and Date: 2009-11-26
• [Remarks] プレスリリース「「海馬」形成の遺伝子特定」、中日新聞、2009年9月24日
• [Remarks] 「記憶つかさどる「海馬」形成遺伝子発見」、朝日新聞、2009年9月24日