Mechanisms and physiological roles of voltage-sensing phosphatase

2010 Fiscal Year Final Research Report

• Project Area: Molecular interaction and modal shift of cellular sensors
• Project/Area Number: 18077013
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University (2008-2010); National Institutes of Natural Sciences Okazaki Research Facilities (2006-2007)
• Principal Investigator: OKAMURA Yasushi 大阪大学, 医学系研究科, 教授 (80201987)
• Co-Investigator(Kenkyū-buntansha): HIGASHIJIMA Shinichi 自然科学研究機構, 生理学研究所, 准教授 (80270479) ; OKOCHI Yoshifumi 大阪大学, 医学系研究科, 助教 (90435818) ; IWASAKI Hirohide 自然科学研究機構, 生理学研究所, 助教 (30342752)
• Project Period (FY): 2006 – 2010
• Keywords: イオンチャネル / 酵素 / シグナル伝達 / 脂質

Research Abstract

Voltage sensing phosphatase gene is conserved in genomes from sea squirt to human. VSP consists of the voltage sensing domain and the cytoplasmic enzyme region that operates as the phosphoinositide phosphatase. Mechanisms of VSP have been examined by integrative approaches including electrophysiology, in vitro phosphatase assay, mathematical modeling analysis and imaging analysis. Results showed that voltage sensor activates PI(4,5)P2 and PIP3 phosphatase activity upon depolarization and this coupling occurs over the entire range of voltage sensitivity of the voltage sensor. We also found that the state of enzyme affects the motions of the voltage sensor suggesting the presence of retrograde interaction from enzyme to the voltage sensor.

Research Products

• [Journal Article] Coupling of the phosphatase activity of Ci-VSP to its voltage sensor activity over the entire range of voltage sensitivity (2011)
  • Author(s): Sakata S, Hossain MI, Okamura Y
  • Journal Title: The Journal of Physiology Volume: 589 Pages: 2687-705
• [Journal Article] Voltage-sensing phosphatase : its molecular relationship with PTEN (2011)
  • Author(s): Okamura Y & Dixon JE
  • Journal Title: Physiology Volume: 26(1) Pages: 6-13
• [Journal Article] Gene expression profile of Ci-VSP in juveniles and adult blood cells of ascidian (2010)
  • Author(s): Ogasawara M, Sasaki M, Nakazawa N, Nishino A & Okamura Y
  • Journal Title: Gene Expression Patterns Volume: 11 Pages: 233-8
• [Journal Article] Voltage-sensing phosphatase : actions and potentials (2009)
  • Author(s): Okamura Y, Murata Y & Iwasaki H
  • Journal Title: J. Physiol. Topical Review Volume: 587(3) Pages: 513-520
• [Journal Article] Enzyme domain affects the movement of the voltage sensor in ascidian and zebrafish VSPs (2008)
  • Author(s): Hossain, M.I., Iwasaki, H., Okochi, Y., Chahine, M., Higashijima, S., Nagayama K. & Okamura, Y.
  • Journal Title: J. Biol. Chem. Volume: 283 Pages: 18248-18259
• [Journal Article] A voltage-sensing phosphatase, Ci-VSP, which shares sequence identity with PTEN, dephosphorylates phosphatidylinositol 4,5-bisphosphate (2008)
  • Author(s): Iwasaki H, Murata Y, Kim Y, Hossain MI, Worby CA, Dixon JE, McCormack T, Sasaki T & Okamura, Y
  • Journal Title: Proc Natl Acad Sci U S A Volume: 105 Pages: 7970-7975
• [Journal Article] Improving membrane voltage measurements using FRET with new fluorescent proteins (2008)
  • Author(s): Tsutsui, H., Karasawa, S., Okamura, Y & Miyawaki, A.
  • Journal Title: Nature Methods Volume: 8 Pages: 683-685
• [Journal Article] Depolarization activates the phosphoinositide phosphatase Ci-VSP, as detected in Xenopus oocytes coexpressing sensors of PIP2 (2007)
  • Author(s): Murata Y & Okamura Y.
  • Journal Title: J. Physiol. Volume: 583 Pages: 875-889
• [Presentation] 電位依存性ホスファターゼVSPの動作原理 特定領域研究 (2010)
  • Author(s): 岡村康司
  • Organizer: 公開シンポジウム細胞感覚 : セルセンサーのモーダルシフト
  • Place of Presentation: 東京
  • Year and Date: 2010-12-23
• [Presentation] 電位感受性ホスファターゼの動作原理と役割 (2010)
  • Author(s): 岡村康司、黒川竜紀、坂田宗平、平郁子、大河内善史、山口真二、小笠原道生、本間光一
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡(シンポジウム)
  • Year and Date: 2010-05-21
• [Presentation] Avian voltage-sensor containing phosphatase provokes the morphological changes in fibroblasts by its phosphatase activity (2009)
  • Author(s): 平郁子、山口真二、山田マミ、神垣ひろこ、黒川竜紀、岡村康司、本間光一
  • Organizer: 第82回日本生化学会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] Visualization of electrical activities with a new voltage probe derived from voltage-sensing phosphatase (2009)
  • Author(s): Tsutsui H, Karasawa S, Miyawaki A, Okamura Y
  • Organizer: 第32回日本神経科学会
  • Place of Presentation: 名古屋(シンポジウム)
  • Year and Date: 2009-09-17
• [Presentation] Mechanisms of physiological roles of voltage sensing proteins without pore structure, Whole Day Symposium, Cell sensors (2009)
  • Author(s): Okamura Y
  • Organizer: 36th International Physiological Society Meeting (IUPS)
  • Place of Presentation: Kyoto(talk)
  • Year and Date: 2009-07-27
• [Presentation] Mechanisms of the voltage-sensor domain proteins (2009)
  • Author(s): Okamura Y
  • Organizer: Harbin Conference on Ion Channels in Technology and Drug Discovery
  • Place of Presentation: Harbin, China
  • Year and Date: 2009-07-15
• [Presentation] Novel roles of voltage sensor domain discovered from ascidian genome : voltage-sensing phosphatase (VSP) and voltage-gated proton channel (VSOP1/Hv1) (2009)
  • Author(s): Sakata S, Okamura Y
  • Organizer: 5th Internatinal Tunicate Meeting
  • Place of Presentation: Okinawa
  • Year and Date: 2009-06-21
• [Presentation] A Voltage Sensitive Phosphatase from Xenopus Laevis Testis (2009)
  • Author(s): Ratzan WJ, Okamura Y, Jaffe LA.
  • Organizer: Biophysical Society 53rd Annual Meeting
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-03-04
• [Presentation] Improved FRET Sensing Of Membrane Voltage With Voltage Sensitive Phosphatase And New Coral Fluorescence Proteins (2009)
  • Author(s): Tsutsui H, Karasawa S, Miyawaki A, Okamura Y.
  • Organizer: Biophysical Society 53rd Annual Meeting
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-03-03
• [Presentation] 高膜電位におけるCi-VSPの電位依存的なホスファターゼ活性の解析 (2008)
  • Author(s): 坂田宗平, Hossain MI, 岡村康司
  • Organizer: 第31回日本神経科学会大会
  • Place of Presentation: 東京(ポスター)
  • Year and Date: 2008-09-13
• [Presentation] ホヤから見いだされた新規電位センサー蛋白 (2008)
  • Author(s): 岡村康司
  • Organizer: 日本動物学会第79回大会シンポジウム「海産動物を用いた基礎生物学エポック研究」
  • Place of Presentation: 福岡
  • Year and Date: 2008-09-05
• [Presentation] 電位センサー蛋白の多様性から見た細胞膜電位シグナル伝達機構の進化 (2008)
  • Author(s): 岡村康司、Thomas McCormack、黒川竜紀、斎藤成也
  • Organizer: 第10回日本進化学会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-08-24
• [Presentation] 電位センサードメインの動作 原理と生理機能 (2008)
  • Author(s): 岡村康司
  • Organizer: 第18回細胞電気薬理学会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-16
• [Presentation] Voltage range for tuning of phosphatase of Ci-VSP as measured by two PIP2-sensors (2008)
  • Author(s): Hossain, M.I., Sakata, S., Murata, Y. & Okamura, Y.
  • Organizer: 52th Biophysical Society Annual Meeting
  • Place of Presentation: Long Beach(USA)(poster)
  • Year and Date: 2008-02-05
• [Presentation] Substrate-dependent structural change of the phosphatasedomain slows the movement of the voltage sensor in 9 voltage-regulatedphosphatases (VSP) (2007)
  • Author(s): Hossain Md I, Higashijima S, Nagayama K, & Okamura Y
  • Organizer: Biophys Society meeting
  • Place of Presentation: Baltimore, USA
  • Year and Date: 20070303-07
• [Presentation] How do animals utilize signals of membrane potentials? : lessons from two voltage-sensing proteins (2007)
  • Author(s): Okamura Y, Sasaki M, Kurokawa T, Okochi Y, Hossain MI, Iwasaki H, Murata Y & Higashijima S
  • Organizer: The 6th Okazaki Biology Conference "Marine Biology"
  • Place of Presentation: Okazaki, Japan
  • Year and Date: 2007-12-04
• [Presentation] Mechanisms of voltage-sensor domain proteins and insights into physiological significance (2007)
  • Author(s): Okamura Y
  • Organizer: Annual Meeting of Neuroscience in Chile
  • Place of Presentation: Los Andes, Chile(Plenary Lecture)
  • Year and Date: 2007-09-27
• [Presentation] Voltage sensor domain proteins (2007)
  • Author(s): Okamura Y
  • Organizer: Ion channel, structure and function, European Biophyics Congress
  • Place of Presentation: London, UK.(Invited talk)
  • Year and Date: 2007-07-16
• [Presentation] 電位依存性ホスファターゼCi-VSPにおける、膜電位感知-酵素活性相関の機構 (2007)
  • Author(s): 村田喜理, 岡村康司
  • Organizer: 第84回日本生理学会大会
  • Place of Presentation: 大阪(Poster)
  • Year and Date: 2007-03-22
• [Presentation] 膜電位シグナルを伝達する新たな膜タンパク質 (2006)
  • Author(s): 岡村康司
  • Organizer: 日本分子生物学フォーラム
  • Place of Presentation: 名古屋
  • Year and Date: 2006-12-08
• [Book] 膜電位情報をイノシトールリン脂質シグナルへ変換する膜タンパク質 VSP, 実験医学増刊「脂質生物学」 (2010)
  • Author(s): 岡村康司
  • Total Pages: 100-105
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/phys2/okamura/index.html
• [Patent(Industrial Property Rights)] NOVELION CHANNEL-LIKEPOLYPEPTIDE AND USE THEREOF (2009)
  • Inventor(s): Noriyuki Satoh, Yasushi Okamura, Hirohide Iwasaki, Yoshimichi Murata
  • Industrial Property Rights Holder: 京都大学、自然科学研究機構
  • Industrial Property Number: 特許権, Patent Number7,592,424
  • Filing Date: 2009-09-22
  • Overseas