Volume-sensor anion channel and mechano-sensor cation channel: Their functional modal shifts and molecular interaction

2010 Fiscal Year Final Research Report

• Project Area: Molecular interaction and modal shift of cellular sensors
• Project/Area Number: 18077008
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: OKADA Yasunobu 生理学研究所, 所長 (10025661)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Nobuyuki 京都大学, 農学研究科, 助教 (50370135) ; INOUE Hana 東京医科大学, 医学部, 助教 (20390700) ; LEE Elbert 米国在住 (30425425) ; NUMATA Tomohiro 京都大学, 工学研究科, 助教 (20455223) ; AKATSUKA Yuhko 鈴鹿医療科学大学, 薬学部薬学科, 准教授 (90321611) ; AKITA Tenpei 生理学研究所, 細胞器官研究系, 特任助教 (00522202)
• Co-Investigator(Renkei-kenkyūsha): OKADA Toshiaki 生理学研究所, 細胞器官研究系, 特任准教授 (00373283)
• Project Period (FY): 2006 – 2010
• Keywords: アニオンチャネル / カチオンチャネル / TRPM7 / モーダルシフト / 蛋白-蛋白相互作用 / メカノセンサー / 容積センサー / ROSセンサー

Research Abstract

Mechano-sensor cation channel TRPM7 and volume-sensor anion channel VSOR play important roles in the cell volume regulation mechanism which determines cell survival and death. The present study showed that TRPM7 exhibits functional modal shifts from a mechano-sensor to an osmo-sensor and a proton-sensor whereas VSOR does so from a volume-sensor to a ROS-sensor and ABC protein-sensor under certain conditions. The present study also showed that TRPM7 interacts with VSOR not only functionally thereby accomplishing cell volume regulation but also molecularly thereby regulating the VSOR activity.

Research Products

• [Journal Article] Involvements of the ABC protein ABCF2 and α-actinin-4 in regulation of cell volume and anion channels in human epithelial cells. (2012)
  • Author(s): Ando-Akatsuka Y, Shimizu T, Numata T, Okada Y.
  • Journal Title: J Cell Physiol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Swelling-activated anion channels are essential for volume regulation of mouse thymocytes. (2011)
  • Author(s): Kurbannazarova RS, Bessonova SV, Okada Y, Sabirov RZ.
  • Journal Title: Int J Mol Sci Volume: 12 Pages: 9125-9137
  • Peer Reviewed
• [Journal Article] Regulation of bradykinin-induced activation of volume-sensitive outwardly rectifying anion channels by Ca^<2+> nanodomains in mouse astrocytes. (2011)
  • Author(s): Akita T, Okada Y.
  • Journal Title: J Physiol Volume: 589 Pages: 3909-3927
  • Peer Reviewed
• [Journal Article] V_2 receptor-mediated autocrine role of somatodendritic release of AVP in rat vasopressin neurons under hypo-osmotic conditions. (2011)
  • Author(s): Sato K, Numata T, Saito T, Ueta Y, Okada Y.
  • Journal Title: Sci Signal Volume: 4 (157), ra5
  • Peer Reviewed
• [Journal Article] Acid-sensing ion channels in rat hypothalamic vasopressin neurons of the supraoptic nucleus. (2010)
  • Author(s): Ohbuchi T, Sato K, Suzuki H, Okada Y, Dayanithi G, Murphy D, Ueta Y.
  • Journal Title: J Physiol Volume: 588 Pages: 2147-62
  • Peer Reviewed
• [Journal Article] Volume-sensitive outwardly rectifying chloride channel in white adipocytes from normal and diabetic mice. (2010)
  • Author(s): Inoue H, Takahashi N, Okada Y, Konishi M.
  • Journal Title: Am J Physiol Cell Physiol Volume: 298 Pages: C900-C909
  • Peer Reviewed
• [Journal Article] Bradykinin-induced astrocyte-neuron signaling: glutamate release is mediated by ROS-activated volume-sensitive outwardly rectifying anion channels. (2009)
  • Author(s): Liu H-T, Akita T, Shimizu T, Sabirov RZ, Okada Y.
  • Journal Title: J Physiol Volume: 587 Pages: 2197-209
  • Peer Reviewed
• [Journal Article] Pathophysiology and puzzles of the volume-sensitive outwardly rectifying anion channel. (2009)
  • Author(s): Okada Y, Sato K, Numata T.
  • Journal Title: J Physiol Volume: 587 Pages: 2141-9
  • Peer Reviewed
• [Journal Article] Proton conductivity through the human TRPM7 channel and its molecular determinants. (2008)
  • Author(s): Numata T, Okada Y
  • Journal Title: J Biol Chem Volume: 283 Pages: 15097-15103
  • Peer Reviewed
• [Journal Article] Molecular determinants of sensitivity and conductivity of human TRPM7 to Mg^<2+> and Ca^<2+>. (2008)
  • Author(s): Numata T , Okada Y
  • Journal Title: Channels Volume: 2 Pages: 283-286
  • Peer Reviewed
• [Journal Article] TRPM7 is a stretch- and swelling-activated cation channel involved in volume regulation in human epithelial cells. (2007)
  • Author(s): Numata T, Shimizu T, Okada Y.
  • Journal Title: Am J Physiol Cell Physiol Volume: 292 Pages: C460-7
  • Peer Reviewed
• [Journal Article] Direct mechano-stress sensitivity of TRPM7 channel. (2007)
  • Author(s): Numata T, Shimizu T, Okada Y.
  • Journal Title: Cell Physiol Biochem Volume: 19 Pages: 1-8
  • Peer Reviewed
• [Presentation] TRPM7 is an essential regulator for the volume-sensitive outwardly rectifying anion channel (VSOR) activity. Abstract p240 (2011)
  • Author(s): Numata T, Sato K, Schmitz C, Hermosura MC, Perraud A-L, Mori Y, Okada Y
  • Organizer: 7th Congress of the Federation of The Asia and Oceanian Physiological Societies (FAOPS 2011)
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 20110911-14
• [Presentation] Volume-regulatory autocrine action of vasopressin released from somato and dendrites in vasopressin neurons is mediated by the V_2 receptor and cAMP. Abstract p16 (2011)
  • Author(s): Sato K, Numata T, Saito T, Ueta Y, Okada Y
  • Organizer: Hydration & Cell Volume Regulation: Cell Volume regulation Meeting 2011
  • Place of Presentation: Tubingen, Germany
  • Year and Date: 20110904-07
• [Presentation] Ca^<2+> nanodomain-mediated regulation of volume-sensitive outwardly rectifying (VSOR) anion channels in mouse astrocytes. Abstract p7 (2011)
  • Author(s): Akita T, Okada Y
  • Organizer: Hydration & Cell Volume Regulation: Cell Volume regulation Meeting 2011
  • Place of Presentation: Tubingen, Germany
  • Year and Date: 20110904-07
• [Presentation] Functional coupling between VSOR Cl^- channel and TRPM7 channel in hypotonic condition in DT40 cells. J. Physiol. Sci. 61 (Suppl 1), S128 (2011)
  • Author(s): Numata T, Sato K, Schmitz C, Hermosura MC, Perraud A-L, Mori Y, Okada Y
  • Organizer: 第88回 日本生理学会大会
  • Place of Presentation: (誌上発表)
  • Year and Date: 20110000
• [Presentation] The role of vasopressin receptor in the AVP neurons under hypotonic conditions. J. Physiol. Sci. 60 (Suppl), S122 (2010)
  • Author(s): Sato K, Numata T, Ueta Y, Okada Y
  • Organizer: 第87回 日本生理学会大会
  • Place of Presentation: 盛岡市民文化ホール・いわて県民情報交流センター, 盛岡
  • Year and Date: 20100519-21
• [Presentation] Reduced expression level of volume-sensitive chloride channel in diabetic adipocytes. J. Physiol. Sci. 60 (Suppl), S105 (2010)
  • Author(s): Inoue H, Takahashi N, Okada Y, Konishi M
  • Organizer: 第87回 日本生理学会大会
  • Place of Presentation: 盛岡市民文化ホール・いわて県民情報交流センター, 盛岡
  • Year and Date: 20100519-21
• [Presentation] Role of the actin cytoskeleton in the interaction between ABCF2 and α-actinin-4. J. Physiol. Sci. 60 (Suppl), S77 (2010)
  • Author(s): Ando-Akatsuka Y, Okada Y
  • Organizer: 第87回 日本生理学会大会
  • Place of Presentation: 盛岡市民文化ホール・いわて県民情報交流センター, 盛岡
  • Year and Date: 20100519-21
• [Presentation] Regulation of bradykinin-induced activation of volume-sensitive outwardly rectifying (VSOR) anion channels via “Ca^<2+> nanodomains” in mouse cortical astrocytes. J. Physiol. Sci. 60 (Suppl), S66 (2010)
  • Author(s): Akita T, Okada Y
  • Organizer: 第87回 日本生理学会大会
  • Place of Presentation: 盛岡市民文化ホール・いわて県民情報交流センター, 盛岡, (シンポジウム口演)
  • Year and Date: 20100519-21
• [Presentation] Bradykinin-induced glutamate release via volume-sensitive outwardly rectifying (VSOR) anion channels in mouse cortical astrocytes. J Physiol Sci 59 Suppl 1 p392 (2009)
  • Author(s): Akita T, Liu H, Sabirov R, Shimizu T, Okada Y
  • Organizer: XXXVI International Congress of Physiological Sciences (IUPS2009)
  • Place of Presentation: Kyoto International Conference Center, Kyoto, Japan
  • Year and Date: 20090727-0801
• [Presentation] Volume-sensitive chloride channel activity in freshly isolated white adipocytes from normal and diabetic mice. J Physiol Sci 59 Suppl 1 p413 (2009)
  • Author(s): Inoue H, Takahashi N, Okada Y, Konishi M
  • Organizer: XXXVI International Congress of Physiological Sciences (IUPS2009)
  • Place of Presentation: Kyoto International Conference Center, Kyoto, Japan
  • Year and Date: 20090727-0801
• [Presentation] Regulatory role of the interaction between ACTN4 and ABCF2 in cell volume regulation and volume-sensitive anion channel. J Physiol Sci 59 Suppl 1 p392 (2009)
  • Author(s): Ando-Akatsuka Y, Shimizu T, Numata T, Mori Y, Okada Y
  • Organizer: XXXVI International Congress of Physiological Sciences (IUPS2009)
  • Place of Presentation: Kyoto International Conference Center, Kyoto, Japan
  • Year and Date: 20090727-0801
• [Presentation] Volume-sensitive chloride channel activity in hippocampal and cortical pyramidal neurons in slice preparation. J. Physiol. Sci. 57 (Suppl), S230 (2007)
  • Author(s): Inoue H, Okada Y
  • Organizer: 第84回 日本生理学会大会
  • Place of Presentation: 大阪国際交流センター, 大阪
  • Year and Date: 20070320-22
• [Presentation] Bradykinin-induced communication between astrocytes and neurons is mediated by glutamate released via volume-sensitive outwardly rectifying anion channels. J. Physiol. Sci. 57 (Suppl), S126 (2007)
  • Author(s): Liu H-T, Sabirov Z, Okada Y
  • Organizer: 第84回 日本生理学会大会
  • Place of Presentation: 大阪国際交流センター, 大阪
  • Year and Date: 20070320-22
• [Presentation] Interaction between ABCF2 and α-actinin-4 is involved in activation of the volume-regulatory anion channel. J. Physiol. Sci. 57 (Suppl), S124 (2007)
  • Author(s): Ando-Akatsuka Y, Shimizu T, Okada Y
  • Organizer: 第84回 日本生理学会大会
  • Place of Presentation: 大阪国際交流センター, 大阪
  • Year and Date: 20070320-22
• [Book] 最新パッチクランプ実験技術法 (2011)
  • Author(s): 岡田泰伸（編著）
  • Total Pages: 274
  • Publisher: 吉岡書店, 京都
• [Book] The puzzles of volume-activated anion channels. In, “Physiology and Pathology of Chloride Transporters and Channels in the Nervous System. From Molecules to Diseases” (eds Alvarez-Leefmans FJ, Delpire E) (2009)
  • Author(s): Okada Y, Sato K, Toychiev AH, Suzuki M, Dutta AK, Inoue H, Sabirov RZ.
  • Total Pages: 283-306
  • Publisher: Elsevier, San Diego
• [Book] Cell volume-sensitive chloride channel: Phenotypic properties and molecular identity. In, “Mechanisms and Significance of Cell Volume Regulation”, (ed. Lang, F.) (2006)
  • Author(s): Okada Y.
  • Total Pages: 9-24
  • Publisher: Karger, Basel
• [Remarks] 読売新聞 朝29面：脳細胞の膨張抑えるホルモン 20110121
• [Remarks] 毎日新聞 夕6面：脳細胞の大きさ調整機能を発見 20110121
• [Remarks] 日本経済新聞 夕14面：神経細胞の膨張を抑制 脳内でもホルモン働く 自然機構、脳浮腫治療に道 20110121
• [Remarks] 中日新聞 朝3面： 脳浮腫抑えるホルモン発見 新療法開発に道 20110122
• [Remarks] 日経産業新聞 10面：脳にも水分調節機能 腎臓と同じ仕組み 20110125
• [Remarks] 科学新聞 4面：抗利尿ホルモン“バソプレシン” 脳内の新たな作用発見 20110204
• [Remarks] 生理学研究所HP＆機能協関研究部門HP：公開日 2012.01.24 細胞容積調節におけるABCF2とα-アクチニン-4の分子間相互作用の役割：Ando-Akatsuka Y, Shimizu T, Numata T, Okada Y. Involvements of the ABC protein ABCF2 and α-actinin-4 in regulation of cell volume and anion channels in human epithelial cells. J Cell Physiol, 2012. (電子版January 2012; doi: 10.1002/jcp.24050)
• [Remarks] 生理学研究所HP＆機能協関研究部門HP：公開日 2011.08.23 Ca^<2+>ナノドメイン」を介する細胞容積センサー外向整流性アニオンチャネル（VSOR）活性化機構の発見：Akita T, Okada Y. Regulation of bradykinin-induced activation of volume-sensitive outwardly rectifying anion channels by Ca^<2+> nanodomains in mouse astrocytes. J Physiol 589: 3909-3927, 2011.
• [Remarks] 生理学研究所HP＆細胞感覚HP：公開日 2011.01.21 利尿を抑えるホルモン"バソプレシン"の脳の中の新たな作用を発見-神経細胞の破裂を防ぎ、その大きさの維持に重要な役割、脳浮腫などの治療法開発に期待―：Sato K, Numata T, Saito T, Ueta Y, Okada Y. V_2 receptor-mediated autocrine role of somatodendritic release of AVP in rat vasopressin neurons under hypo-osmotic conditions. Sci Signal 4: ra5, 2011.
• [Remarks] 生理学研究所HP：公開日 2010.08.20 「脳内乳酸はバソプレッシンの分泌量を増やすようだ！」体内の水分量を調節するホルモン・バソプレッシンを分泌する神経の新たな興奮メカニズムを解明：Ohbuchi T, Sato K, Suzuki H, Okada Y, Dayanithi G, Murphy D, Ueta Y. Acid-sensing ion channels in rat hypothalamic vasopressin neurons of the supraoptic nucleus. J Physiol 588: 2147-62, 2010.
• [Remarks] 生理学研究所HP＆細胞感覚HP：公開日 2009.02.18 容積感受性外向整流性アニオンチャネル(VSOR)を介する炎症時のグリアからニューロンへの情報伝達機構の発見：Liu H-T, Akita T, Shimizu T, Sabirov RZ, Okada Y. Bradykinin-induced astrocyte-neuron signaling: glutamate release is mediated by ROS-activated volume-sensitive outwardly rectifying anion channels. J Physiol (London) 587: 2197-209, 2009.
• [Remarks] 生理学研究所HP＆機能協関研究部門HP：公開日 2008.04.17 プロトンチャネルとしてのTRPM7：その分子基盤：Numata T, Okada Y. Proton conductivity through the human TRPM7 channel and its molecular determinants. J Biol Chem 283, 15097-103, 2008.
• [Remarks] 生理学研究所HP＆機能協関研究部門HP：公開日 2007.04.06 TRPM7は細胞容積調節に関与するメカノセンサーチャネルである：Numata T, Shimizu T, Okada Y. TRPM7 is a stretch- and swelling-activated cation channel involved in volume regulation in human epithelial cells. Am J Physiol Cell Physiol 292: C460-7, 2007；Numata T, Shimizu T, Okada Y. Direct mechano-stress sensitivity of TRPM7 channel. Cell Physiol Biochem 19: 1-8, 2007.