Analyses of an orphan metabotropic receptor which plays a role in the long term retention of memory, and a secretory protein encoded by its splice variant

• Project/Area Number: 26293044
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: KUBO Yoshihiro 生理学研究所, 分子細胞生理研究領域, 教授 (80211887)
• Co-Investigator(Kenkyū-buntansha): 今野 幸太郎 北海道大学, 医学(系)研究科(研究院), 助教 (20599641)
• Co-Investigator(Renkei-kenkyūsha): YAMAMOTO Izumi 生理学研究所, 分子生理研究系, 特別研究員 (20645254) ; WATANABE Masahiro 北海道大学, 医学(系)研究科(研究院), 教授 (70210945)
• Research Collaborator: Chen I-Shan 生理学研究所, 特任助教 ; Yamamoto Tomomi 生理学研究所, 技術職員 ; TATEYAMA Michihiro 生理学研究所, 准教授 ; TAKAO Keizo 生理学研究所, 特任准教授 ; MIYAKAWA Tsuyoshi 藤田保健衛生大学, 教授 ; HATTORI Satoko 藤田保健衛生大学, 助教 ; FUKATA Masaki 生理学研究所, 教授 ; FUKATA Yuko 生理学研究所, 准教授 ; YOKOI Norihiko 生理学研究所, 助教 ; SAKIMURA Kenji 新潟大学, 脳研究所, 教授 ; SYUU Rei 新潟大学, 脳研究所, ポスドク研究員 ; NATSUME Rie 新潟大学, 脳研究所, 技術職員
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2016: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: Prrt3 / オーファン受容体 / スプライス異型 / 恐怖条件付け記憶 / 長期保持 / オーファン代謝型受容体 / 網羅的行動解析 / 代謝型受容体

Outline of Final Research Achievements

Prrt3 is a putative G protein coupled receptor of family C, but its function is totally unknown. We aimed at the elucidation of the molecular function and physiological role of Prrt3, and observed the followings. (1) Prrt3 is partly cleaved at the end of N-terminal extracellular domain by Furin. (2) It binds to glutamate transporters EAAT1, 2 and Gi/o G protein. (3) It is expressed chiefly at the presynaptic terminal of excitatory neurons. (4) Conditional Prrt3 gene knock out homozygous mice in forebrain excitatory neurons showed impairment of long term retention of fear conditioning memory. (5) Prtt3 is activated by Oxo-M, a muscarinic Ach receptor agonist, but not by ACh.

Research Products

• [Journal Article] Stabilizing effects of G protein on the active conformation of adenosine A1 receptor differ depending on G protein type (2016)
  • Author(s): Tateyama M, Kubo Y
  • Journal Title: European Journal of Pharmacology Volume: 788 Pages: 122-131
  • DOI: 10.1016/j.ejphar.2016.06.025
  • Peer Reviewed
• [Presentation] Behavioral analyses of forebrain specific knock-out mice of an orphan metabotropic receptor Prrt3 and screening of small molecule library toward identification of its ligand (2017)
  • Author(s): Chen IS, Yamamoto T, Zhou Li, Natsume R, Konno K, Uesugi M, Watanabe M, Takao K, Miyakawa T, Sakimura K, Kubo Y
  • Organizer: 第40回日本神経科学大会
  • Place of Presentation: 千葉県、幕張市、幕張メッセ
  • Year and Date: 2017-07-20
• [Presentation] Effects and activation mechanisms of antiparasitic agents on GIRK channels (2017)
  • Author(s): Chen IS, Kubo Y
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: 静岡県、浜松市、アクトシティ浜松
  • Year and Date: 2017-03-28
• [Presentation] Activation mechanisms of an orphan metabotropic receptor Prrt3 (2016)
  • Author(s): 陳以珊、山本友美、久保義弘
  • Organizer: 第93回 日本生理学会
  • Place of Presentation: 札幌コンベンションセンター（北海道、札幌市）
  • Year and Date: 2016-03-22
• [Presentation] LC-MS/MS analysis of an orphan metabotropic receptor Prrt3 complex (2015)
  • Author(s): 山本泉、横井紀彦、深田優子、今野幸太郎、山本友美、渡辺雅彦、深田正紀、久保義弘
  • Organizer: 第92回 日本生理学会大会
  • Place of Presentation: 神戸国際会議場（兵庫県、神戸市）
  • Year and Date: 2015-03-21
• [Presentation] An investigation of post-translational cleavage of an orphan metabotropic receptor, Prrt3. (2014)
  • Author(s): 山本泉、山本友美、今野幸太郎、渡辺雅彦、久保義弘
  • Organizer: 第37回 日本神経科学大会
  • Place of Presentation: パシィフィコ横浜（神奈川県、横浜市）
  • Year and Date: 2014-09-11