Functional characterization of redox-sensitive ion channels usingchemical library

• Project/Area Number: 22681033
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Living organism molecular science
• Research Institution: Kyoto University
• Principal Investigator: KIYONAKA Shigeki 京都大学, 地球環境学堂, 准教授 (90422980)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥25,740,000 (Direct Cost: ¥19,800,000、Indirect Cost: ¥5,940,000); Fiscal Year 2012: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2011: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2010: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
• Keywords: TRPチャネル / レドックス / カルシウムチャネル / ケミカルライブラリー / ケミカルライブラリ

Research Abstract

In mammals, it is essential for our life to sense intracellular redox status. Recently, a class of TRP channels has been demonstrated to act as cell sensors for various environmental changes. In this research, we constructed chemical library having various redox properties to precisely characterize the redox sensitivity of TRP channels. Our characterization identified that TRPA1 is a highly sensitive channel for oxidation and reduction. Importantly, TRPA1 channel is activated by molecular oxygen, and critically contributes to oxygen-sensing mechanisms in mice.

Research Products

• [Journal Article] Physical and Functional Interaction of the Active Zone Protein CAST/ERC2 and the β-subunit of the Voltage-dependent Ca2+Channel. (2012)
  • Author(s): Kiyonaka S
  • Journal Title: J. Biochem Volume: 152 Issue: 2 Pages: 149-159
  • DOI: 10.1093/jb/mvs054
  • NAID: 10031166124
  • Peer Reviewed
• [Journal Article] Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy. (2012)
  • Author(s): Tadmouri A, Kiyonaka S
  • Journal Title: EMBO J Volume: 31 Pages: 3730-3744
  • Peer Reviewed
• [Journal Article] Physical and functional interaction of the active zone protein CAST/ERC2 and the β-subunit of the voltage-dependent Ca(2+) channel. (2012)
  • Author(s): Kiyonaka S
  • Journal Title: Jouronal of Biochemistry Volume: 152 Pages: 149-159
  • NAID: 10031166124
  • Peer Reviewed
• [Journal Article] Cacnb4 directly couples electrical activity to gene expression, a process defective in juvenile epilepsy. (2012)
  • Author(s): Tadmouri A
  • Journal Title: The EMBO journal Volume: 31 Issue: 18 Pages: 3730-3744
  • DOI: 10.1038/emboj.2012.226
  • Peer Reviewed
• [Journal Article] TRPA1 underlies a sensing mechanism for O_2 (2011)
  • Author(s): Takahashi N, Kuwaki K, Kiyonaka S, Numata T, Kozai D, Mizuno Y, Yamamoto S, Naito S, Knevels E, Carmeliet P, Oga T, Kaneko S, Suga S, Nokami T, Yoshida J & Mori Y
  • Journal Title: Nature Chem. Biol. Volume: 7 Issue: 10 Pages: 701-711
  • DOI: 10.1038/nchembio.640
  • Peer Reviewed
• [Journal Article] Genetic and Pharmacologic Inhibition of the Ca2+Influx Channel TRPC3 Protects Secretory Epithelia From Ca2+-Dependent Toxicity. (2011)
  • Author(s): Kim MS, Lee KP, Yang D, Shin DM, Abramowitz J, Kiyonaka S
  • Journal Title: Gastroenterology Volume: 140 Issue: 7 Pages: 2107-2115
  • DOI: 10.1053/j.gastro.2011.02.052
  • Peer Reviewed
• [Journal Article] TRPC3-mediated Ca^<2+> influx contributes to Rac1-mediated production of reactive oxygen species in MLP-deficient mouse hearts (2011)
  • Author(s): Kitajima N, Watanabe K, Morimoto S, Sato Y, Kiyonaka S, Hoshijima M, Ikeda Y, Nakaya M, Ide T, Mori Y, Kurose H, Nishida M
  • Journal Title: Biochem.Biophys.Res.Commun. Volume: 409 Issue: 1 Pages: 108-113
  • DOI: 10.1016/j.bbrc.2011.04.124
  • Peer Reviewed
• [Journal Article] The juvenile myoclonicepilepsy-related protein EFHC1 interacts with the redox-sensitive TRPM2 channel linked to cell death (2011)
  • Author(s): Katano M, Aguan K, Hara Y, Yamamoto S, Miki T, Sawamura S, Suzuki T, Yamakawa K & Mori Y
  • Journal Title: Cell Calcium Volume: (in press) Issue: 2 Pages: 179-185
  • DOI: 10.1016/j.ceca.2011.12.011
  • Peer Reviewed
• [Journal Article] Genetic and Pharmacologic Inhibition of the Ca2+ Influx Channel TRPC3 Protects Secretory Epithelia From Ca2+-Dependent Toxicity (2011)
  • Author(s): Kim MS, Lee KP, Yang D, Shin DM, Abramowitz J, Kiyonakas, 他3人
  • Journal Title: Gastroenterology Volume: 140 Pages: 2107-2115
  • Peer Reviewed
• [Journal Article] Ca^<2+> influx and protein scaffolding via TRPC3 sustain PKCβand ERK activation in B cells (2010)
  • Author(s): Numaga T, Nishida M, Kiyonaka S, Kato K, Katano K, Mori E, Kurosaki T, Inoue R, Hikida T, Putney Jr JW & Mori M
  • Journal Title: J. Cell Sci. Volume: 123 Issue: 6 Pages: 927-938
  • DOI: 10.1242/jcs.061051
  • Peer Reviewed
• [Journal Article] Inhibition of TRPC6 channel activity contributes to the anti-hypertrophic effects of natriuretic peptides-guanylyl cyclase-Asignaling in the heart (2010)
  • Author(s): Kinoshita H, Kuwahara K, Nishida M, Jiang Z, Rong X, Kiyonaka S, Kuwabara Y, Kurose H, Inoue R, Mori Y, Li Y, Nakagawa Y, Usami S, Fujiwara M, Yamada Y, Minami T, Ueshima K & Nakao K
  • Journal Title: Circ. Res. Volume: 106 Issue: 12 Pages: 1849-1860
  • DOI: 10.1161/circresaha.109.208314
  • Peer Reviewed
• [Journal Article] Rab3-interacting moleculer isoforms lacking the Rab3-binding domain induce long lasting currents but blockneurotransmitter vesicle anchoring in voltage-dependent P/Q-type Ca^<2+> channels (2010)
  • Author(s): Uriu Y, Kiyonaka S, Miki T, Yagi M, Akiyama S, Mori E, Nakao A, Beedle AM, Campbell KP, Wakamori M, Mori Y
  • Journal Title: J Biol Chem Volume: 285 Issue: 28 Pages: 21750-21767
  • DOI: 10.1074/jbc.m110.101311
  • Peer Reviewed
• [Journal Article] RIM γ isoforms lacking the Rab3-binding domain induce long-lasting currents but block neurotransmitter vesicle-anchoring in voltage-dependent P/Q-type Ca^<2+> channels (2010)
  • Author(s): Uriu Y, Kiyonaka S, 他9人
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 21750-21767
  • Peer Reviewed
• [Journal Article] Ca^<2+> influx and protein scaffolding via TRPC3 sustain PKCβ and ERK activation in B cells (2010)
  • Author(s): Numaga T, Nishida M, Kiyonaka S, 他9人
  • Journal Title: J.Cell Sci. Volume: 123 Pages: 927-938
  • Peer Reviewed
• [Journal Article] Molecular determinants for cardiovascular TRPC6 channel regulation by Ca2+/calmodulin-dependent kinase II.
  • Author(s): Shi J, Geshi N, Takahashi S, Kiyonaka S
  • Journal Title: J. Physiol Volume: (in press)
  • Peer Reviewed
• [Presentation] LDAI化学の新展開:神経伝達物質受容体のケミカルラベル (2013)
  • Author(s): 瓜生幸嗣、清中茂樹、浜地格
  • Organizer: 、日本化学会第93春季年会
  • Place of Presentation: 立命館大学(滋賀県草津市)
  • Year and Date: 2013-03-23
• [Presentation] 神経伝達物質受容体のケミカルラベル (2013)
  • Author(s): 若山 翔
  • Organizer: 日本化学会第93春季年会
  • Place of Presentation: 立命館大学（滋賀県）
• [Presentation] RIM family forms protein complexes with voltage-dependent Ca2+channels. (2011)
  • Author(s): Kiyonaka S, Mori Y.
  • Organizer: 1st international meeting on ion channel signaling mechanisms.
  • Place of Presentation: Marrakesh, Morocco.
  • Year and Date: 2011-11-01
• [Presentation] RIM family forms protein complexes with voltage-dependent Ca2+ channels (2011)
  • Author(s): Kiyonaka S
  • Organizer: 1st international meeting on ion channel signaling mechanisms
  • Place of Presentation: Marrakesh, Morocco
• [Presentation] Rab3結合領域を持たないγ-RIMはP/Q型電位依存性Ca2+チャネルの電流を持続させ、小胞のアンカーリングを阻害する、 (2010)
  • Author(s): 瓜生幸嗣、清中茂樹(他9人)
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-12-07
• [Presentation] Rab3結合領域を持たないγ-RIMは、P/Q型電位依存性Ca2+チャネルの電流を持続させ、小胞のアンカーリングを阻害する (2010)
  • Author(s): 瓜生幸嗣、清中茂樹, 他9人
  • Organizer: 第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド(神戸市)
  • Year and Date: 2010-12-07