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2011 Fiscal Year Final Research Report

On the mechanism of modal regulation of cardiovascular Ca2+entry channel TRPC6

Research Project

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Project/Area Number 21590246
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionFukuoka University

Principal Investigator

INOUE Ryuji  福岡大学, 医学部, 教授 (30232573)

Project Period (FY) 2009 – 2011
KeywordsCa^<2+>チャネル / TRP蛋白質 / リン酸化 / 受容体・機械刺激 / 形質転換 / 活性化モード / 細胞骨格 / 蛋白質間相互作用
Research Abstract

The canonical transient receptor potential protein 6(TRPC6) is a Ca^<2+> entry channel activated by synergistic operation of receptor-mediated and mechanosentive signaling pathways. Its excessive activity contributes to the pathogenesis of cardiovascular diseases. The results of the present study suggest that the synergy between receptor and mechanical stimulations on TRPC6 channel activation likely occurs through physical interaction and functional coupling between TRPC6 channel N-terminal ankyrin-like domains and actin cytoskeleton. Further, this synergy is exaggerated by pathogenic mutations in amino acid residues adjacent to these domains, and counteracted byprotein kinase G-mediated phosphorylation of TRPC6 N-terminus, by strengthening and disrupting the N-terminus domain-actin cytoskeleton interaction, respectively.

  • Research Products

    (57 results)

All 2012 2011 2010 2009 Other

All Journal Article (17 results) (of which Peer Reviewed: 15 results) Presentation (36 results) Book (3 results) Remarks (1 results)

  • [Journal Article] Critical Role of TRPC1-mediated Ca^<2+> entry in Decidualization of Human Endometrial Stromal Cells2012

    • Author(s)
      Kawarabayashi Y, Hai L, Honda A, Horiuchi S, Tsujioka H, Inoue R.
    • Journal Title

      Mol Endocrinol

      Volume: 26(5) Pages: 846-858

    • DOI

      DOI:10.1210/me2011-1259

    • Peer Reviewed
  • [Journal Article] A Self-limiting Regulation of vasoconstrictor-activated TRPC3/C6/C7 Channels Coupled with PI(4, 5) P_2-Diacylglycerol Signaling2012

    • Author(s)
      Imai Y, Itsuki K, Okamura Y, Inoue R, Mori MX.
    • Journal Title

      Journal of Physiology(Lond)

      Volume: 590 Pages: 1101-1119

    • DOI

      DOI:10.1113/jphysiol.2011.2213589

    • Peer Reviewed
  • [Journal Article] BKCa and KV channels limit conducted vasomotor responses in rat mesenteric terminal arterioles2011

    • Author(s)
      Hald BO, Jacobsen JCB, Braunstein TH, Inoue R, Ito Y, Sorensen PG, Holstein-Rathlou NH, Jensen LJ.
    • Journal Title

      Pflugers Archiv Eur J Physiol

      Volume: 463(2) Pages: 279-95

    • DOI

      DOI:10.1007/s00424-011-1049-8

    • Peer Reviewed
  • [Journal Article] Counteracting effect of TRPC1-associated Ca^<2+> influx on TNFα-induced COX-2-dependent prostaglandin E_2 production in human colonic myofibroblasts2011

    • Author(s)
      Hai L, Kawarabayashi Y, Imai Y, Honda A, Inoue R.
    • Journal Title

      American Journal of Physiology-Gastrointestinal and Liver Physiology

      Volume: 301(2) Pages: G356-67

    • DOI

      DOI:10.1152/ajpgi.00354.2010

    • Peer Reviewed
  • [Journal Article] Quantitative measurement of intracellular Ca^<2+> and calmodulin binding to target molecules using Fura-2 and CFP/YFP based FRET imaging in living cells2011

    • Author(s)
      Mori MX, Imai Y, Itsuki K, Inoue R.
    • Journal Title

      Biochemistry

      Volume: 50(21) Pages: 4685-96

    • DOI

      DOI:10.1021/bi200287x

    • Peer Reviewed
  • [Journal Article] Cilostazol Suppresses Angiotensin II-Induced Vasoconstriction via Protein Kinase A-Mediated Phosphorylation of the Transient Receptor Potential Canonical 6 Channel2011

    • Author(s)
      Nishioka K, Nishida M, Ariyoshi M, Jian Z, Saiki S, Hirano M, Nakaya M, Sato Y, Kita S, Iwamoto T, Hirano K, Inoue R, Kurose H.
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 31 Pages: 2278-2286

    • DOI

      DOI:10.1161/ATVBAHA.110.221010

    • Peer Reviewed
  • [Journal Article] Dualsignaling pathways of arterial constriction by extracellular UTP in the rat2011

    • Author(s)
      Sugihara M, Morita H, Matsuda M, Umebayashi H, Kajioka S, Ito S, Nishida M, Inoue R, Futatsuki T, Yamazaki J, Mori Y, Inoue R, Ito Y, Abe K, Hirata M.
    • Journal Title

      J Pharmacol Sci

      Volume: 115(3) Pages: 293-308

    • DOI

      DOI:10.1254/jphs.10281FP

    • Peer Reviewed
  • [Journal Article] Regulation of cardiovascular TRP channel functions along the NO-cGMP-PKG axis2010

    • Author(s)
      Inoue R, Shi J, Jian Z, ImaiY.
    • Journal Title

      Exp Rev Clin Pharmacol

      Volume: 3(3) Pages: 347-360

    • DOI

      DOI:10.1586/ecp.10.15

    • Peer Reviewed
  • [Journal Article] Inhibition of TRPC6 Channel Activity contributes to the Anti-hypertrophic Effects of Natriuretic Peptides-guanylyl cyclase-A signaling in the heart2010

    • Author(s)
      Kinoshita H, Kuwahara K, Nishida M, Zhong J, Rong X, Kiyonaka S, Kuwabara Y, Kurose H, Inoue R, et al.
    • Journal Title

      Circ Res

      Volume: 106(12) Pages: 1849-1860

    • DOI

      doi:10.1161/CIRCRESAHA.109.208314

    • Peer Reviewed
  • [Journal Article] Phosphorylation of TRPC6 channels at Thr^<69> is required for anti-hypertrophic effects of phosphodiesterase 5 inhibition2010

    • Author(s)
      Nishida M, Watanabe K, Satob Y, Nakaya M, Kitajima N, Ide T, Inoue R, Kurose H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 285(17) Pages: 13244-13253

    • DOI

      DOI:10.1074/jbc.M109.074104

    • Peer Reviewed
  • [Journal Article] Ca^<2+> Influx and protein scaffolding via TRPC3 sustain PKCβ and ERK activation in B cells2010

    • Author(s)
      Numaga T, Nishida M, Kiyonaka S, Kato K, Katano M, Mori E, Kurosaki T, Inoue R, Hikida M, Putney JWJr, Mori Y.
    • Journal Title

      J Cell Sci

      Volume: 123(6) Pages: 927-938

    • DOI

      doi:10.1242/jcs.061051

    • Peer Reviewed
  • [Journal Article] Mechanosensitive TRP channels in cardiovascular pathophysiology2009

    • Author(s)
      Inoue R, Jian Z, Kawarabayashi Y.
    • Journal Title

      Pharmacol Ther

      Volume: 123 Pages: 371-385

    • DOI

      10.1016/j.pharmthera.2009.05.009

    • Peer Reviewed
  • [Journal Article] Synergistic activation of vascular TRPC6 channel by receptor and mechanical stimulation via PLC/diacylglycerol and PLA2/ω-hydroxylase/20-HETE pathways2009

    • Author(s)
      Inoue R, Jensen LJ, Jian Z, Shi J, Hai L, Lurie AI, Henriksen FH, Salmonsson M, Morita H, Kawarabayashi Y, Mori M, Mori Y, Ito Y.
    • Journal Title

      Circ Res

      Volume: 104 Pages: 1399-1409

    • DOI

      DOI:10.CIRCRESAHA.108.193227

    • Peer Reviewed
  • [Journal Article] 17β-estradiol-induced enhancement of estrogen receptor biosynthesis via MAPK pathway in mouse skeletal muscle myoblasts2009

    • Author(s)
      Hatae J, Takami N, Lin H, Honda A, Inoue R.
    • Journal Title

      J Physiol Scis

      Volume: 59(3) Pages: 181-90

    • DOI

      DOI:10.1007/s12576-009-0023-0

    • Peer Reviewed
  • [Journal Article] 受容体・機械刺激協働による心血管Ca^<2+>流入チャネルTRPC6の活性化増幅機構2009

    • Author(s)
      井上隆司、森誠之、瓦林靖広、菅忠
    • Journal Title

      日本薬理学会誌

      Volume: 134 Pages: 116-121

  • [Journal Article] 血圧調節とTRPチャネル2009

    • Author(s)
      井上隆司、海琳、波多江純眞
    • Journal Title

      日本自律神経学会誌

      Volume: 第46巻、第3号 Pages: 198-206

  • [Journal Article] 心血管TRPチャネルを巡る病態生理の新展開2009

    • Author(s)
      井上隆司、瓦林精広、森誠之
    • Journal Title

      日本心電図学会誌(Jpn. J. Electrocardiology)

      Volume: 29, Suppl. 5 Pages: S-5-9-S-5-19

    • Peer Reviewed
  • [Presentation] I型cGMP依存性キナーゼのロイシンジッパー領域を介したTRPC6との相互作用の解析2012

    • Author(s)
      本田啓、井上隆司
    • Organizer
      第89回日本生理学会大会
    • Place of Presentation
      松本
    • Year and Date
      20120329-30
  • [Presentation] A self-limiting regulation of TRPC3/C6/C7 channels coupled with PIP2-DAG signaling2012

    • Author(s)
      Imai Y, Itsuki K, Okamura Y, Inoue R, Mori MX.
    • Organizer
      Biophysical Society 56th Annual Meeting
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      20120225-29
  • [Presentation] 膜脂質とリン酸化によるTRPCチャネルを介したCa情報伝達制御機構2012

    • Author(s)
      井上隆司
    • Organizer
      蔵王カンファレンス(招待講演)
    • Place of Presentation
      山形
    • Year and Date
      2012-01-27
  • [Presentation] PIP2の枯渇によるTRPC6抑制機構の作用基盤とその生理的意義2011

    • Author(s)
      今井裕子、齊郷平、岡村康司、井上隆司、森誠之
    • Organizer
      第62回西日本生理学会
    • Place of Presentation
      佐賀
    • Year and Date
      20111014-15
  • [Presentation] PIP2-DAGシグナルによるTRPC3/6/7チャネル制御キネティクスの差異2011

    • Author(s)
      齊郷平、今井裕子、岡村康司、森誠之、井上隆司
    • Organizer
      第62回西日本生理学会
    • Place of Presentation
      佐賀
    • Year and Date
      20111014-15
  • [Presentation] Autonomic regulation of TRPC3/C6/C7-channels coupled with PI(4, 5) P2-DAG signaling2011

    • Author(s)
      Imai Y, Mori M, Itsuki K, Inoue R.
    • Organizer
      The 7th FAOPS(Congress of the Federation of Asian and Oceanian Physiological Societies)
    • Place of Presentation
      Taiwan
    • Year and Date
      20110911-14
  • [Presentation] PI(4, 5) P2-PLC-DAGシグナルと連繋したTRPC3/6/7チャネルの自律的制御機構2011

    • Author(s)
      今井裕子、齊郷平、森誠之、岡村康司、井上隆司
    • Organizer
      第88回日本生理学会大会
    • Place of Presentation
      横浜
    • Year and Date
      20110328-30
  • [Presentation] I型cGMP依存性キナーゼはサブタイプ特異的な方法でTRPC6のN末領域と相互作用する2011

    • Author(s)
      本田啓、菅忠、倉原(海)琳、井上隆司
    • Organizer
      第88回日本生理学会大会
    • Place of Presentation
      横浜
    • Year and Date
      20110328-30
  • [Presentation] I型cGMP依存性キナーゼのC末領域は基質結合に対するcGMP依存性に寄与している2011

    • Author(s)
      本田啓、井上隆司
    • Organizer
      日本農芸化学会2011年度大会
    • Place of Presentation
      京都
    • Year and Date
      20110326-28
  • [Presentation] cGMP/PKG系の活性化は家族性単状分節性糸球体硬化症と関連したTRPC6チャネル変異体の機能亢進を抑制する2011

    • Author(s)
      市川純、井上隆司
    • Organizer
      第84回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      20110322-24
  • [Presentation] 心血管病態におけるTRPチャネルの役割2011

    • Author(s)
      井上隆司
    • Organizer
      横浜市立大学医学部セミナー(招待講演)
    • Place of Presentation
      東京
    • Year and Date
      2011-12-22
  • [Presentation] TRPC3/C6/C7チャネルにおけるPIP2に対するサブタイプ特異的感受性と不活性化相関2011

    • Author(s)
      斎郷平、今井裕子、岡村康司、井上隆司、森誠之
    • Organizer
      生理研研究会「心血管イオンチャネル・トランスポーター研究の新展開」
    • Place of Presentation
      岡崎
    • Year and Date
      2011-11-30
  • [Presentation] Mechanosensitive TRP channels in cardiovascular function and disease2011

    • Author(s)
      Inoue R, Hu Y, Duan Y, Imai Y, Itsuki K.
    • Organizer
      International Symposium on Mechanobiology(5th Shanghai International Conference on Biophysics and Molecular biology)
    • Place of Presentation
      Shanghai, China
    • Year and Date
      2011-11-05
  • [Presentation] 心血管系における受容体・機械刺激活性化Ca^<2+>流入の分子病態生理学的意義2011

    • Author(s)
      井上隆司
    • Organizer
      第28回日本医学会総会5-S-6シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2011-04-09
  • [Presentation] 膜脂質メッセンジャーを介した受容体・機械刺激Ca2+応答の統合制御機構2011

    • Author(s)
      井上隆司、今井裕子、齊郷平、市川純、森誠之
    • Organizer
      第88回日本生理学会大会(シンポジウム:細胞内脂質メディエーターの細胞機能疾患)
    • Place of Presentation
      横浜
    • Year and Date
      2011-03-29
  • [Presentation] Analysis of the interaction between TRPC6 and PKG type I by site directed mutagenesis2010

    • Author(s)
      Honda A, Inoue R.
    • Organizer
      The 9th Japan-Korea Joint Symposium on Brain Sciences, and Cardiac and Smooth Muscles
    • Place of Presentation
      鹿児島
    • Year and Date
      20101125-27
  • [Presentation] 単状分節性糸球体硬化症の原因遺伝子となるTRPC6チャネル変異体の機能解析とアクチン骨格の関連2010

    • Author(s)
      市川純、井上隆司
    • Organizer
      第20回日本循環薬理学会
    • Place of Presentation
      札幌
    • Year and Date
      20101111-12
  • [Presentation] ホスホイノシチド代謝と連動したTRPC6チャネルの自律的制御2010

    • Author(s)
      今井裕子、森誠之、岡村康司、井上隆司
    • Organizer
      第61回西日本生理学会
    • Place of Presentation
      長崎
    • Year and Date
      20101015-16
  • [Presentation] 単状分節性糸球体硬化症の原因遺伝子としてのTRPC6チャネル変異体の機能解析2010

    • Author(s)
      市川純、井上隆司
    • Organizer
      第61回西日本生理学会
    • Place of Presentation
      長崎
    • Year and Date
      20101015-16
  • [Presentation] TRPC6チャネルN末領域に存在するI型PKGとの相互作用部位の探索2010

    • Author(s)
      本田啓、菅忠、井上隆司
    • Organizer
      第61回西日本生理学会
    • Place of Presentation
      長崎
    • Year and Date
      20101015-16
  • [Presentation] 単状分節性糸球体硬化症の原因遺伝子となるTRPC6チャネル変異体は受容体刺激に対し過剰な応答を示す2010

    • Author(s)
      市川純、井上隆司
    • Organizer
      第63回日本薬理学会西南部会
    • Place of Presentation
      鹿児島
    • Year and Date
      2010-11-26
  • [Presentation] Functional elucidation ot TRPC6 channel mutations associated with familial focal segmental glomeruloscerosis(FSGS)2010

    • Author(s)
      Ichikawa J, Inoue R.
    • Organizer
      The 9th Japan-Korea Joint Symposium on Brain Sciences, and Cardiac and Smooth Muscles
    • Place of Presentation
      鹿児島
    • Year and Date
      2010-11-26
  • [Presentation] Quantitative semi-simultaneous imaging of Ca^<2+> and Ca^<2+-> dependent calmodulin interactions by FRET interaction by FRET2010

    • Author(s)
      Mori M, Imai Y, Itsuki K, Inoue R.
    • Organizer
      The 9th Japan-Korea Joint Symposium on Brain Sciences, and Cardiac and Smooth Muscles
    • Place of Presentation
      鹿児島
    • Year and Date
      2010-11-26
  • [Presentation] 心血管CaチャネルTRPC6の機能と制御-受容体・機械刺激応答性のリン酸化を介した統合的制御機構-2010

    • Author(s)
      井上隆司
    • Organizer
      第13回札幌高血圧セミナー(招待講演)
    • Place of Presentation
      札幌
    • Year and Date
      2010-07-09
  • [Presentation] Regulation of TRPC channe ; s by phosphoinositides(PIPs) and calmodulin2010

    • Author(s)
      Imai Y, Mori M, Okamura Y, Inoue R.
    • Organizer
      第87回日本生理学会大会シンポジウム
    • Place of Presentation
      盛岡
    • Year and Date
      2010-05-21
  • [Presentation] YTRPC6 N-terminal 136 amino acid region contributes to the interaction with PKG type 12010

    • Author(s)
      Honda A, Jian Z, Hai L, Takahashi S, Inoue R.
    • Organizer
      第87回日本生理学会大会
    • Place of Presentation
      盛岡
    • Year and Date
      2010-05-20
  • [Presentation] Acute dephosphorylation of PIPs leads to transient inactivation of the TRPC6 channel2010

    • Author(s)
      Imai Y, Mori M, Okamura Y, Inoue R.
    • Organizer
      第87回日本生理学会大会
    • Place of Presentation
      盛岡
    • Year and Date
      2010-05-20
  • [Presentation] Semi-simultaneous imaging fro linkage to basal Ca^<2+> and ion channel regulations through calmodulin2010

    • Author(s)
      Mori M, Imai Y, Inoue R.
    • Organizer
      第87回日本生理学会大会シンポジウム
    • Place of Presentation
      盛岡
    • Year and Date
      2010-05-19
  • [Presentation] PKG-mediated phosphorylation as a molecular switch for mechanical and receptor-mediated activation of vascular Ca^<2+> entry channel TRPC62009

    • Author(s)
      Jian Z, Inoue R.
    • Organizer
      Annual Meeting of Tokyo Biochemical Research Foundation
    • Place of Presentation
      東京
    • Year and Date
      2009-12-14
  • [Presentation] NO/cGMP/PKGによる血管受容体作動性TRPC6チャネルの活性化調節分子機構2009

    • Author(s)
      海琳、菅忠、高橋眞一、本田啓、森誠之、井上隆司
    • Organizer
      第19回日本循環薬理学会
    • Place of Presentation
      京都
    • Year and Date
      2009-11-27
  • [Presentation] PKGリン酸化を介したTRPC6チャネル活性化モードの短長期制御機構2009

    • Author(s)
      井上隆司、菅忠、瓦林靖広、本田啓
    • Organizer
      第60回西日本生理学会
    • Place of Presentation
      福岡
    • Year and Date
      2009-11-06
  • [Presentation] 細胞内カルシウムとCa^<2+>チャネル-Calmodulin作用の準同時的イメージング2009

    • Author(s)
      森誠之、今井裕子、井上隆司
    • Organizer
      第60回西日本生理学会
    • Place of Presentation
      福岡
    • Year and Date
      2009-11-06
  • [Presentation] Involvement of transient receptor potential(TRP) channels in vasodilation by cilostazol2009

    • Author(s)
      Nishioka K, Ariyoshi M, Inoue R, Nakaya M, Nishida M, Kurose H.
    • Organizer
      The 36^<th> Congress of the International Union of Physiological Sciences(IUPS2009)
    • Place of Presentation
      Kyoto
    • Year and Date
      2009-07-31
  • [Presentation] Fundamental molecular mechanism of TRPC6 channel with calmodulin interaction2009

    • Author(s)
      Mori MX, Inoue R.
    • Organizer
      The 36^<th> Congress of the International Union of Physiological Sciences(IUPS2009)
    • Place of Presentation
      Kyoto
    • Year and Date
      2009-07-30
  • [Presentation] PKG type I negatively regulates TRPC6 by phosphorylation through interaction with TRPC6 N terminal domain2009

    • Author(s)
      Honda A, Jian Z, Hai L, Takahashi S, Inoue R.
    • Organizer
      The 36^<th> Congress of the International Union of Physiological Sciences(IUPS2009)
    • Place of Presentation
      Kyoto
    • Year and Date
      2009-07-28
  • [Presentation] PKGリン酸化による血管作動性Ca^<2+>チャネルTRPC6チャネル活性化モード転換機構2009

    • Author(s)
      井上隆司、菅忠、瓦林靖広、本田啓
    • Organizer
      第51回平滑筋学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-07-23
  • [Book] Lipid-mediated mechanisms involved in the mechanical activation of TRPC6 and TRPV4 channels in the vascular tone regulation. In :"Mechanosensitivity in Cells and Tissues. Volume, No 6.-Mechanically Gated Channels and their regulation-"2012

    • Author(s)
      Inoue R, Hu Y, Duan Y, Itsuki K.
    • Publisher
      Springer Verlag
  • [Book] The pathophysiological implications of TRP channels in cardiac arrhythmia. In :"Cardiac Arrhythmias ? New Considerations-". Ed. Francisco R. Breijo-Marquez2012

    • Author(s)
      Inoue R, Duan Y, Hu Y, Ichikawa J.
    • Total Pages
      978-953-51-0126-0
    • Publisher
      InTech Review-Open Access Publisher
  • [Book] TRP channels and blood pressure regulation. In : TRP channel in health and disease : Implications for Diagnosis and Therapy. ed., A. Szallasi.2011

    • Author(s)
      Inoue R, Shi J.
    • Total Pages
      171-196
    • Publisher
      Nova Science Publishers
  • [Remarks]

    • URL

      http://www.med.fukuoka-u.ac.jp/physiol/index-j.htm

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Published: 2013-07-31  

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