Regulatory mechanism of diverse G protein signaling in cortical development

• Project/Area Number: 24590113
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Aomori University (2014); Nara Institute of Science and Technology (2012-2013)
• Principal Investigator: MIZUNO Norikazu 青森大学, 薬学部, 教授 (90212232)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: シグナル伝達 / 神経科学 / 脳・神経 / 薬学

Outline of Final Research Achievements

To analyze the regulatory mechanisms of diverse G protein signaling in cortical development, (1) we investigated the function of Ric-8A/B, which are novel non-receptor type G protein regulators, in neural stem cells. We found that Ric-8A/B was related to the neural stem cell proliferation, and more, Ric-8B was involved in the facilitatory effect of Gs signaling on the cell migration. (2) We generated the functional antibodies against human GPR56, which inhibited the glioma cell migration. These antibodies revealed that human GPR56 inhibited the cell migration through Gq/Rho pathways.

Research Products

• [Journal Article] Agonistic Antibodies Reveal the Function of GPR56 in Human Glioma U87-MG Cells (2015)
  • Author(s): Ohta S, Sakaguchi S, Kobayashi Y, Mizuno N, Tago K, Itoh H.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 38 Issue: 4 Pages: 594-600
  • DOI: 10.1248/bpb.b14-00752
  • NAID: 130005062265
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increased ubiquitination and the crosstalk of G protein signaling in cardiac myocytes: Involvement of Ric-8B in Gs suppression by Gq signal (2013)
  • Author(s): Riris Jenie, Motoki Nishimura, Mika Fujino, Michio Nakaya, Norikazu Mizuno, Kenji Tago, Hitoshi Kurose & Hiroshi Itoh.
  • Journal Title: Genes to Cells Volume: 18 Issue: 12 Pages: 1095-1106
  • DOI: 10.1111/gtc.12099
  • Peer Reviewed
• [Journal Article] Maintenance of the hematopoietic stem cell pool in bone marrow niches by EVI1-regulated GPR56 (2013)
  • Author(s): Saito Y., Kaneda K., Suekane A., Ichihara E., Nakahata S., Yamakawa N., Nagai K., Mizuno N., Kogawa K., Miura I., Itoh H., and Morishita K..
  • Journal Title: Leukemia Volume: 27 Issue: 8 Pages: 1637-1649
  • DOI: 10.1038/leu.2013.75
  • Peer Reviewed
• [Journal Article] Phosphorylation of doublecortin by protein kinase A orchestrates microtubule and actin dynamics to promote neuronal progenitor cell migration (2012)
  • Author(s): Toriyama M, Mizuno N, Fukami T, Iguchi T, Toriyama M, Tago K, Itoh H
  • Journal Title: J. Biol Chem Volume: 287 Issue: 16 Pages: 12691-12702
  • DOI: 10.1074/jbc.m111.316307
  • Peer Reviewed
• [Presentation] 機能抗体を用いた癌細胞におけるGPR56の機能解析 (2014)
  • Author(s): 水野憲一、太田茂之、小林祐希、坂口さやか、伊東 広
  • Organizer: 第66回日本細胞生物学会大会
  • Place of Presentation: 奈良
  • Year and Date: 2014-06-10 – 2014-06-12
• [Presentation] 心筋細胞でのGqシグナルによるGs抑制機構に対するRic-8Bの関与 (2013)
  • Author(s): 水野 憲一, Riris Istighfari Jenie, 仲矢 道雄, 多胡 憲治, 黒瀬 等, 伊東 広
  • Organizer: 第86回日本生化学会
  • Place of Presentation: 横浜
• [Presentation] 神経細胞の分化に伴うGPR56の発現パターンの変化 (2013)
  • Author(s): 野島 悠佑, 水野 憲一, 伊東 広
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸
• [Presentation] LGR5の発現とシグナル伝達の解析 (2013)
  • Author(s): 根岩 直希, 水野 憲一, 小林 哲夫, 伊藤 友里, 伊東 広
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸
• [Remarks] 分子情報薬理学 (伊東研究室)
  • URL: http://bsw3.naist.jp/itoh/