Molecular basis underlying the generation of spatiotemporal patterns of cytosolic calcium dynamics

• Project/Area Number: 20370054
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: MICHIKAWA Takayuki The Institute of Physical and Chemical Research, 発生神経生物研究チーム, 副チームリーダー (90282516)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥20,670,000 (Direct Cost: ¥15,900,000、Indirect Cost: ¥4,770,000); Fiscal Year 2010: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2009: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2008: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
• Keywords: カルシウムシグナル / 細胞内情報伝達 / セカンドメッセンジャー / イノシトール三リン酸 / カルシウム放出チャネル / カルシウムポンプ / ホスフォリパーゼC / カルシウム振動 / システムズバイオロジー / 情報伝達 / 蛍光共鳴エネルギー移動 / イオンチャネル / カルシウム

Research Abstract

The gating mechanism of inositol 1,4,5-trisphosphate receptor (IP_3R)/Ca^<2+> release channels and the Ca^<2+> pump activity of sarco/endoplasmic reticulum Ca^<2+> ATPase during Ca^<2+> oscillations were investigated by using the fluorescent resonance energy transfer technique. Phospholipase C β1 and β4 were identified to be crucial for the generation of Ca^<2+> oscillations in HeLa cells stimulated with histamine. We constructed a mathematical model to reproduce Ca^<2+> and IP_3 dynamics observed and found that a dual-ligand competition of IP_3R is a fundamental mechanism for the generation of Ca^<2+> oscillations.

Research Products

• [Journal Article] Highly cooperative dependence of sarco/endoplasmic reticulum calcium ATPase (SERCA) 2a pump activity on cytosolic calcium in living cells (2011)
  • Author(s): Satoh K., Matsu-ura T., Enomoto M., Nakamura H., Michikawa T., Mikoshiba K.
  • Journal Title: J.Biol.Chem. (in press)
  • Peer Reviewed
• [Journal Article] Functional characterization of the P1059L mutation in the inositol 1,4,5-trisphosphate receptor type 1 identified in a Japanese SCA15 family (2011)
  • Author(s): Yamazaki H., Nozaki H., Onodera O., Michikawa T., Nishizawa M., Mikoshiba K.
  • Journal Title: Biochem.Biophys.Res.Commun. (in press)
  • Peer Reviewed
• [Journal Article] Tyr-167/Trp-168 in type 1/3 inositol ,4,5-trisphosphate receptor mediates functional coupling between ligand binding and channel opening (2010)
  • Author(s): Yamazaki H., Chan J., Ikura M., Michikawa T., Mikoshiba K.
  • Journal Title: J.Biol.Chem. 285 Pages: 36081-36091
  • Peer Reviewed
• [Journal Article] Structural studies of inositol 1,4,5-trisphosphate receptor: coupling ligand binding to channel gating (2010)
  • Author(s): Chan J., Yamazaki H., Ishiyama N., Seo M-D., Mal T.K., Michikawa T., K.Mikoshiba, Ikura M.
  • Journal Title: J.Biol.Chem. 285 Pages: 36092-36099
  • Peer Reviewed
• [Journal Article] Spontaneous network activity visualized by ultrasensitive Ca^<2+> indicator, yellow Cameleon-Nano (2010)
  • Author(s): Hirokawa K., Yamada Y., Matsuda T., Kobayashi K., Hashimoto M., Matsu-ura T., Miyawaki A., Michikawa T., Mikoshiba K., Nagai T.
  • Journal Title: Nat.Methods. 7 Pages: 729-732
  • NAID: 120002834691
  • Peer Reviewed
• [Journal Article] Tyr-167/Trp-168 in type 1/3 inositol 1,4,5-trisphosphate receptor mediates functional coupling between ligand binding and channel opening (2010)
  • Author(s): Yamazaki, H., et al.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 36081-36091
  • Peer Reviewed
• [Journal Article] Structural studies of inositol 1,4,5-trisphosphate receptor : coupling ligand binding to channel gating (2010)
  • Author(s): Chan, J., et al.
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 36092-36099
  • Peer Reviewed
• [Journal Article] Spontaneous network activity visualized by ultrasensitive Ca^<2+> indicator, yellow Cameleon-Nano (2010)
  • Author(s): Horikawa, K., et al.
  • Journal Title: Nat.Methods Volume: 7 Pages: 729-732
  • Peer Reviewed
• [Journal Article] ATP modulation of Ca^<2+> release by type-2 and type-3 inositol (1,4,5)-trisphosphate receptors. Differing ATP sensitivities and molecular determinants of action (2008)
  • Author(s): Betzenhauser M.J., Wagner L.E., Iwai M., Michikawa T., Mikoshiba K., Yule D.
  • Journal Title: J.Biol.Chem. 283 Pages: 21579-21587
  • Peer Reviewed
• [Journal Article] ATP modulation of Ca2+ release by type-2 and type-3 inositol (1, 4, 5)-triphosphate receptors. Differing ATP sensitivities and molecular determinants of action (2008)
  • Author(s): Betzenhauser MJ, et al.
  • Journal Title: J Biol Chem 283 Pages: 21579-87
  • Peer Reviewed
• [Presentation] The relationship between IP3 level and the frequency of Ca^<2+> oscillations (2011)
  • Author(s): Toru Matsu-ura, Sachiko Ishida, Takayuki Michikawa, Katsuhiko Mikoshiba
  • Organizer: Biophysical Society 55th Annual Meeting
  • Place of Presentation: Baltimore, MD, USA
• [Presentation] Highly cooperative dependence of SERCA2a calcium pump activity on cytosolic caclium (2011)
  • Author(s): Kanayo Satoh, Toru Matsu-ura, Masahiro Enomoto,Takayuki Michikawa, Katsuhiko Mikoshiba
  • Organizer: Biophysical Society 55th Annual Meeting
  • Place of Presentation: Baltimore, MD, USA
• [Presentation] The relationship between IP_3 level and the frequency of Ca^<2+> oscillations (2011)
  • Author(s): 松浦徹
  • Organizer: Biophysical Society 55th Annual Meeting
  • Place of Presentation: Baltimore, USA
• [Presentation] Analysis of the regulatory mechanism of Ca^<2+> oscillations with a novel IP_3R model that reproduces cytosolic IP_3 dynamics (2010)
  • Author(s): 松浦徹
  • Organizer: 第83回日本生化学会大会・第33回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] Evaluation of the performance of genetically encoded calcium indicators expressed in mammalian neurons (2010)
  • Author(s): 山田義之
  • Organizer: Neuroscience 2010
  • Place of Presentation: San Diego, USA
  • Year and Date: 2010-11-17
• [Presentation] Analysis of the regulatory mechanism of Ca^<2+> oscillations with a novel IP3R model that reproduces cytosolic IP3 dynamics (2010)
  • Author(s): Toru Matsu-ura, Sachiko Ishida,Takayuki Michikawa,Katsuhiko Mikoshiba
  • Organizer: 第83回日本生化学会大会・第33回日本分子生物学会年会合同大会
  • Place of Presentation: 神戸
• [Presentation] Evaluation of the performance of genetically encoded calcium indicators expressed in mammalian neurons (2010)
  • Author(s): Yoshiyuki. Yamada,Takayuki Michikawa,Mitsuhiro Hashimoto, Atsushi Miyawaki, Michael Hausser, Katsuhiko Mikoshiba
  • Organizer: Neuroscience2010
  • Place of Presentation: San Diego, CA USA
• [Presentation] Evaluating the performance of genetically encoded calcium indicators expressed in mammalian neurons (2010)
  • Author(s): Yoshiyuki Yamada,Takayuki Michikawa,Mitsuhiro hashimoto, Atsushi Miyawaki, Katsuhiko Mikoshiba
  • Organizer: Neuro2010第33回日本神経科学大会・第53回日本神経化学会大会・第20回日本神経回路学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] Distinct roles of phospholipase C beta1 and beta4 in the generation of Ca^<2+> oscillations (2010)
  • Author(s): Sachiko Ishida, Taru Matsu-ura,Takayuki Michikawa,Katsuhiko Mikoshiba
  • Organizer: 第48回生物物理学会
  • Place of Presentation: 仙台
• [Presentation] 蛍光タンパク質Ca<2+>センサーによる哺乳類神経細胞の活動記録法 (2010)
  • Author(s): 山田義之
  • Organizer: Neuro2010
  • Place of Presentation: 神戸
• [Presentation] Ca^<2+>振動形成におけるホスホリパーゼCβ1およびβ4の異なる役割 (2010)
  • Author(s): 石田幸子
  • Organizer: 第48回生物物理学会年会
  • Place of Presentation: 仙台
• [Presentation] イノシトール三リン酸受容体カルシウム放出チャネルの開口機構の解析 (2009)
  • Author(s): 山崎美佳、道川貴章、御子柴克彦
  • 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] イノシトール三リン酸受容体カルシウム放出チャネルの開口機構の解析 (2009)
  • Author(s): 山崎美佳、道川貴章、御子柴克彦
  • Organizer: 第82回日本生化学会年会
  • Place of Presentation: 神戸
• [Presentation] An adenovirus-based novel experimental system for introduction of genetically encoded tools (2009)
  • Author(s): Yoshiyuki Yamada,Takayuki Michikawa,Mitsuhiro Hashimoto, Atsushi Miyawaki, Katsuhiko Mikoshiba
  • Organizer: 第32回日本神経科学会大会
  • Place of Presentation: 名古屋
• [Presentation] カルシウム振動の周期はどのように調節されているのか (2008)
  • Author(s): 松浦徹、道川貴章、御子柴克彦
  • Organizer: 第81回日本生化学会合同大会、第31回日本分子生物学会
  • Place of Presentation: 神戸
• [Book] Methods Mol.Biol.(Isolation of inositol 1,4,5-trisphosphate receptor-associating proteins and selective knockdown using RNA interference 645) (2010)
  • Author(s): Mizutani A., Kawaai K., Hisatsune C., Ando H., Michikawa T., Mikoshiba K.
• [Book] Isolation of inositol 1,4,5-trisphosphate receptor-associating proteins and selective knockdown using RNA interference. Methods in Molecular Biology : Inositol Phosphates and Lipids (2010)
  • Author(s): Mizutani, A., et al.
  • Total Pages: 230
  • Publisher: Humana Press Inc.
• [Book] Isolation of inositol 1,4,5-trisphosphate receptor-associating proteins and selective knockdown using RNA interference. Methods in Molecular Biology : Inositol Phosphates and Lipids
  • Author(s): Mizutani, A., et al.
  • Publisher: Humana Press Inc.(印刷中)