Analysis of GPCR signaling in cortical development using the functional antibody

• Project/Area Number: 21590094
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: MIZUNO Norikazu 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (90212232)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 神経科学 / 脳・神経 / 薬学

Research Abstract

Using the functional antibodies against the neural progenitor cell-specific G protein coupled receptors(GPCRs), we investigated the function and the signal transduction of these GPCRs in cortical development. We elucidated that Gs-PKA signaling regulated the phosphorylation of doublecortin that induced the lamellipodium formation and neural progenitor cell migration, while Gq and G12/13 signals inhibited the migration.

Research Products

• [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 Pages: 1261-12702
  • 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
• [Journal Article] Structural basis for the specific inhibition of heterotrimeric Gq protein by a small molecule (2010)
  • Author(s): Nishimura A, Kitano K, Takasaki J, Taniguchi M, Mizuno N, Tago K, Hakoshima T, Itoh H
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 107 Pages: 13666-13671
  • Peer Reviewed
• [Journal Article] kB-Ras is a nuclear-cytoplasmic small GTPase that inhibits the NF-kB activation through the suppression of transcriptional activation of p65/RelA (2010)
  • Author(s): Tago K, Funakoshi-Tago M, Sakinawa M, Mizuno N, Itoh H
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 30622-30633
  • Peer Reviewed
• [Journal Article] Ric-8B stabilizes the alpha subunit of stimulatory G protein by inhibiting its ubiquitination (2010)
  • Author(s): Nagai Y, Nishimura A, Tago K, Mizuno N, Itoh H
  • Journal Title: J Biol Chem Volume: 285 Pages: 11114-111120
  • Peer Reviewed
• [Journal Article] Structural basis for the specific inhibition of heterotrimeric Gq protein by a small molecule (2010)
  • Author(s): Nishimura A, Kitano K, Takasaki J, Taniguchi M, Mizuno N, Tago K, Hakoshima T, Itoh H.
  • Journal Title: Proc Natl Acad Sci USA Volume: 107 Pages: 13666-13671
  • Peer Reviewed
• [Journal Article] kB-Ras is a nuclear-cytoplasmic small GTPase that inhibits the NF-kB activation through the suppression of transcriptional activation of p65/RelA (2010)
  • Author(s): Tago K, Funakoshi-Tago M, Sakinawa M, Mizuno N, Itoh H.
  • Journal Title: J Biol Chem Volume: 285 Pages: 30622-30633
  • Peer Reviewed
• [Journal Article] Ric-8B stabilizes the alpha subunit of stimulatory G protein by inhibiting its ubiquitination. (2010)
  • Author(s): Nagai Y, Nishimura A, Tago K, Mizuno N, Itoh H.
  • Journal Title: J Biol Chem. 285 Pages: 11114-111120
  • Peer Reviewed
• [Journal Article] G-protein signalling negatively regulates the stability of aryl hydrocarbon receptor (2009)
  • Author(s): Nakata A, Urano D, Fujii-Kuriyama Y, Mizuno N, Tago K, Itoh H
  • Journal Title: EMBO Rep Volume: 10 Pages: 622-628
  • Peer Reviewed
• [Journal Article] G-protein signalling negatively regulates the stability of aryl hydrocarbon receptor. (2009)
  • Author(s): Nakata A, Urano D, Fujii-Kuriyama Y, Mizuno N, Tago K, Itoh H.
  • Journal Title: EMBO Rep. 10 Pages: 622-628
  • Peer Reviewed
• [Presentation] Analysis of non-receptor type of G protein regulator Ric-8 involved in Drosophila gastrulation (2011)
  • Author(s): Kenta Takami
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2011-12-16
• [Presentation] N-terminal fragment of Latrophilin1 negatively regulates the adheison GPCR-induced signals (2011)
  • Author(s): Naoto Sasai
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2011-12-16
• [Presentation] Involvement of Ric-8 in the Gαq-induced supression of Gs signaling (2011)
  • Author(s): Riris Jenie
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2011-12-16
• [Presentation] Functional involvement of an atypical nuclear-cytoplasmic small GTPas kB-Ras in oncogenic signaling pathway (2011)
  • Author(s): Kenji Tago
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2011-12-16
• [Presentation] Functional involvement of an atypical nuclear-cytoplasmic small GTPaskB-Ras in oncogenic signaling pathway (2011)
  • Author(s): Kenji Tago, Megumi Funakoshi-Tago, Yoichiro Fukao, Naoyuki Sugiyama, Masaru Tomita, Norikazu Mizuno, Hiroshi Itoh
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2011-12-16
• [Presentation] Doublecortin orchestrates microtubule and actin dynamics to promote neuronal progenitor cell migration in a manner dependent on phosphorylation by PKA (2011)
  • Author(s): Manami Toriyama
  • Organizer: 2011 Annual meeting, ASCB
  • Place of Presentation: DENVER, USA.
  • Year and Date: 2011-12-04
• [Presentation] Doublecortin orchestrates microtubule and actin dynamics to promote neuronal progenitor cell migration in a manner dependent on phosphorylation by PKA (2011)
  • Author(s): Manami Toriyama, Norikazu Mizuno, Tokuichi Iguchi, Michinori Toriyama, Takashi Fukami, Kenji Tago, Hiroshi Itoh
  • Organizer: 2011 Annual meeting, ASCB
  • Place of Presentation: DENVER, U.S.A.
  • Year and Date: 2011-12-04
• [Presentation] Gタンパク質シグナルにより制御されるSUMO化とその分子機構の解析 (2011)
  • Author(s): 多胡憲治
  • Organizer: 第84回日本生化学会
  • Place of Presentation: 京都府京都市
  • Year and Date: 2011-09-24
• [Presentation] 微小菅結合タンパク質doublecortinのPKAによるリン酸化を介した新規アクチン骨格制御 (2011)
  • Author(s): 鳥山真奈美
  • Organizer: 第84回日本生化学会
  • Place of Presentation: 京都府京都市
  • Year and Date: 2011-09-24
• [Presentation] Gs-PKAシグナルによる微小管結合タンパク質doublecortinの新規機能の獲得 (2011)
  • Author(s): 鳥山真奈美
  • Organizer: 第58回日本生化学会近畿支部例会
  • Place of Presentation: 大阪守口市
  • Year and Date: 2011-05-21
• [Presentation] Glycosylation of GPR56 extracellular domain affects on the signaling and the GPS cleavage (2011)
  • Author(s): Shigeyuki Ota
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 神奈川県横浜市
• [Presentation] Multi-regulation of neuronal progenitor migration by G protein signaling American Society for Neurochemistry (2011)
  • Author(s): Norikazu Mizuno
  • Organizer: 42nd Annual Meeting
  • Place of Presentation: St. Louis, Missouri USA
• [Presentation] Phosphorylation of doublecortin by G protein-PKA signaling regulatesneuronal progenitor cell migration American Society for Neurochemistry (2011)
  • Author(s): Manami Toriyama
  • Organizer: 42nd Annual Meeting
  • Place of Presentation: St. Louis, Missouri USA
• [Presentation] Glycosylation of GPR56 extracellular domain affects on the signaling and the GPS cleavage (2011)
  • Author(s): Shigeyuki Ota
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 神奈川県横浜市(ポスター)(口頭)
• [Presentation] Multi-regulation of neuronal progenitor migration by G protein signaling (2011)
  • Author(s): Norikazu Mizuno, Manami Thriyama, Kenji Tago, Hiroshi Itoh.
  • Organizer: American Society for Neurochemistry 42nd Annual Meeting
  • Place of Presentation: St.Louis, Missouri U.S.A
• [Presentation] Phosphorylation of doublecortin by G protein-PKA signaling regulatesneuronal progenitor cell migration (2011)
  • Author(s): Manami Toriyama, Norikazu Mizuno, Kenji Tago, Hiroshi Itoh.
  • Organizer: American Society for Neurochemistry 42nd Annual Meeting
  • Place of Presentation: St.Louis, Missouri U.S.A
• [Presentation] Doublecortinのリン酸化を介したGs-PKAシグナルによる神経前駆細胞の遊走促進 (2010)
  • Author(s): 鳥山真奈美
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2010-12-10
• [Presentation] Doublecortinのリン酸化を介したGs-PKAシグナルによる神経前駆細胞の遊走促進 (2010)
  • Author(s): 鳥山真奈美、水野憲一、多胡憲治、伊東広
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会(BMB2010)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] 大脳皮質形成における神経前駆細胞移動のG蛋白質シグナルによる多重制御機構 (2010)
  • Author(s): 水野憲一
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会(BMB2010)
  • Place of Presentation: 兵庫県神戸市
• [Presentation] 大脳皮質形成における神経前駆細胞移動のG蛋白質シグナルによる多重制御機構 (2010)
  • Author(s): 水野憲一、鳥山真奈美、多胡憲治、伊東広
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会(BMB2010)
  • Place of Presentation: 神戸
• [Presentation] Ric-8B accelerates Gs signaling through the stabilization of the a subunit of stimulatory G protein The American Society for Cell Biology (2009)
  • Author(s): Yusuke Nagai
  • Organizer: 49th annual meeting
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2009-12-07
• [Presentation] Ric-8B accelerates Gs signaling through the stabilization of the a subunit of stimulatory G protein (2009)
  • Author(s): Yusuke Nagai, Akiyuki Nishimura, Kenji Tago, Norikazu Mizuno, Hiroshi Itoh
  • Organizer: The American Society for Cell Biology 49th annual meeting
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2009-12-07
• [Presentation] 三量体Gタンパク質Gαsのユビキチン化はRic-8Bとの結合により抑制される (2009)
  • Author(s): 永井裕介
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2009-10-24
• [Presentation] 三量体Gタンパク質Gαsのユビキチン化はRic-8Bとの結合により抑制される (2009)
  • Author(s): 永井裕介、西村明幸、多胡憲治、水野憲一、伊東広
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2009-10-24
• [Presentation] Gタンパク質シグナルによるdoublecortinのリン酸化と細胞遊走の解析 (2009)
  • Author(s): 吉田真奈美
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2009-10-22
• [Presentation] Gタンパク質シグナルによるdoublecortinのリン酸化と細胞遊走の解析 (2009)
  • Author(s): 吉田真奈美、水野憲一、多胡憲治、伊東広
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2009-10-22
• [Book] LANDES BIOSCIENCE Adhesion. GPCRs Structure to Function (2010)
  • Author(s): Norikazu Mizuno, and Hiroshi Itoh
• [Book] Adhesion GPCRs Structure to Function CHAPTER 14 : Signal transduction mediated through adhesion GPCRs (2010)
  • Author(s): Norikazu Mizuno, Hiroshi Itoh
  • Total Pages: 9
  • Publisher: LANDES BIOSCIENCE
• [Remarks]
  • URL: http://bsw3.naist.jp/itoh/
• [Remarks]
  • URL: http://bsw3.naist.jp/itoh/