Regulation of aquaporin-4 by formation of protein complex and orthogonal array

• Project/Area Number: 21390061
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General physiology
• Research Institution: Keio University
• Principal Investigator: YASUI Masato 慶應義塾大学, 医学部, 教授 (90246637)
• Co-Investigator(Kenkyū-buntansha): NAKAO Kazuki 独立行政法人理化学研究所, 動物実験支援ユニット, ユニットリーダー (20217657)
• Co-Investigator(Renkei-kenkyūsha): ABE Yoichiro 慶應義塾大学, 医学部, 助教 (10317331) ; YUKUTAKE Yoshinori 慶應義塾大学, 医学部, 助教 (80449016)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2011: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2009: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: アクアポリン / 蛋白複合体 / 構造機能相関 / 水分子 / 脳浮腫 / 非線形光学 / コンピューターシミュレーション

Research Abstract

To investigate physiological roles of square array formation of aquaporin-4 (AQP4) in vivo, we established two kinds of AQP4 knockout mice: M1 isoform-specific KO, which is expected to possess much larger arrays than wild type, and null mice. As a result of comprehensive phenotype analysis, we found that appropriate size of the square arrays is essential for the retinal response to light stimulation. In addition, we demonstrated that AQP4 plays an important role for immunological function in the central nervous system by making stub-wounded model using AQP4-null mice. Both types of knockout mice have been deposited at RIKEN BRC so as to be used freely by other researchers.

Research Products

• [Journal Article] Establishment of Monoclonal antibodies against the extracellular domain that block binding of NMO-IgG to AQP4 (2013)
  • Author(s): Miyazaki K, Abe Y, Iwanari H, Suzuki Y, Kikuchi T, Ito T, Kato J, Kusano-Arai O, Takahashi T, Nishiyama S, Ikeshima-Kataoka H, Tsuji S, Arimitsu T, Kato Y, Sakihama T, Toyama Y, Fujihara K, Hamakubo T and Yasui M
  • Journal Title: J. Neuroimmunol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Immunological function of aquaporin-4 in stab-wounded mouse brain in concert with a pro-inflammatory cytokine inducer, osteopontin (2013)
  • Author(s): Ikeshima-Kataoka H, Abe Y, Abe T, and Yasui M
  • Journal Title: Mol. Cell. Neurosci Volume: (in press)
  • Peer Reviewed
• [Journal Article] An astrocyte-specific enhancer of aquaporin-4 gene functions through a consensus sequence of POU transcription factors in concert with multiple upstream elements (2012)
  • Author(s): Abe Y, Ikeshima-Kataoka H, Goda W, Niikura T, and Yasui M
  • Journal Title: J. Neurochem Volume: 120(6) Pages: 899-912
  • Peer Reviewed
• [Journal Article] An astrocyte-specific enhancer of aquaporin-4 gene functions through a consensus sequence of POU transcription factors in concert with multiple upstream elements (2012)
  • Author(s): Abe Y, Ikeshima-Kataoka H, Goda W, Niikura T., Yasui M
  • Journal Title: J.Neurochem Volume: 120(6) Pages: 899-912
  • Peer Reviewed
• [Journal Article] Quiescence and _YH2AX in Neuroblastoma are Regulated by Ouabain/Na, K-ATPase (2012)
  • Author(s): Hiyoshi H, Abdelhady S, Segerstrom L, Sveinbjornsson B, Nuriya M, Lundgren T.K, Desfrere L, Miyakawa A, Yasui M, Kogne P, Johnsen J.I, Andang M, Uhlen P
  • Journal Title: British Journal of Cancer Volume: (in press)
  • Peer Reviewed
• [Journal Article] Apoptosis in mouse amniotic epithelium is induced by activated macrophages through the TNF receptor type 1/TNF pathway (2011)
  • Author(s): Kobayashi K, Umezawa K., Yasui M.
  • Journal Title: Biology of Reproduction Volume: 84 Pages: 248-54
  • Peer Reviewed
• [Journal Article] Progesterone maintains amniotic tight junctions during midpregnancy in mice (2011)
  • Author(s): Kobayashi K, Miwa H., Yasui M
  • Journal Title: Mol Cell Endocrinol Volume: 337(1-2) Pages: 36-42
  • Peer Reviewed
• [Journal Article] Curcumin and genistein additively potentiate G551D-CFTR (2011)
  • Author(s): Yu YC*, Miki H*, Nakamura Y, Hanyuda A, Matsuzaki Y, Abe Y, Yasui M, Tanaka K, Hwang TC, Bompadre SB., Sohma Y (*co-first authors)
  • Journal Title: Journal ot Cystic Fibrosis Volume: 10(4) Pages: 243-52
  • Peer Reviewed
• [Journal Article] Plasma membrane aquaporin AqpZ is essential for glucose metabolism during photomixotrophic growth of Synechocystis sp.PCC 6803 (2011)
  • Author(s): Akai M, Onai K, Kusano M, Sato M, Redestig H, Toyooka K, Morishita M, Miyake H, Hazama A, Checchetto V, Szabo I, Matsuoka K, Saito K, Yasui M, Ishiura M., Uozumi N
  • Journal Title: Journal of Biological Chemistry Volume: 286(28) Pages: 25224-35
  • Peer Reviewed
• [Journal Article] Non-Gaussian Fluctuations Resulting from Power-Law Trapping in a Lipid Bilayer (2011)
  • Author(s): Akimoto T, Yamamoto E, Yasuoka K, Hirano Y., Yasui M
  • Journal Title: Phys.Rev.Lett. Volume: 107(17) Pages: 178103-7
  • Peer Reviewed
• [Journal Article] Analysis of Aquaporin-Mediated Diffusional Water Permeability by Coherent Anti-Stokes Raman Scattering Microscopy (2011)
  • Author(s): Ibata K, Takimoto S, Morisaku T, Atsushi Miyawaki., Yasui M
  • Journal Title: Biophys J Volume: 101(9) Pages: 2277-2283
  • Peer Reviewed
• [Journal Article] Regulation of water permeability through aquaporin-4 (2010)
  • Author(s): Yukutake, Y., Yasui, M.
  • Journal Title: Neuroscience (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Molecular Mechanisms How Mercury Inhibits Water Permeation of Aquaporin-1 : Understanding by Molecular Dynamics Simulation (2010)
  • Author(s): Hirano Y, Okimoto N, Yasuoka K, Taiji M, Suematsu M, Yasui M
  • Journal Title: Biophys.J. (in press)
  • Peer Reviewed
• [Journal Article] Expression and distribution of tight junction proteins in human amnion during late pregnancy (2010)
  • Author(s): Kobayashi, K., Kadohira, I., Tanaka, M., Yoshimura, Y., Ikeda, K., Yasui, M.
  • Journal Title: Placenta 31 Pages: 158-162
  • Peer Reviewed
• [Journal Article] Regulation of Kv2.1 phosphorylation in an animal model of anoxia (2010)
  • Author(s): Ito T, Nuriya M, Yasui M.
  • Journal Title: Neurobiol.Dis. 38 Pages: 85-91
  • Peer Reviewed
• [Journal Article] Activity-dependent regulation of HCN1 protein in cortical neurons (2009)
  • Author(s): Arimitsu T, Nuriya M, Ikeda K, Takahashi T, Yasui M
  • Journal Title: Biochem.Biophys.Res.Commun. 387 Pages: 87-91
  • Peer Reviewed
• [Journal Article] Drosophila big brain does not act as a water channel, but mediates cell adhesion (2009)
  • Author(s): Tatsumi K, Tsuji S, Miwa H, Morisaku T, Nuriya M, Orihara M, Kaneko K, Okano H, Yasui M.
  • Journal Title: FEBS Lett. 583 Pages: 2077-2082
  • Peer Reviewed
• [Journal Article] TSHR Mutations as a Cause of Congenital Hypothyroidism in Japan : a Population-Based Genetic Epidemiology Study (2009)
  • Author(s): Narumi S, Muroya K, Abe Y, Yasui M, Asakura Y, Adachi M, Hasegawa T
  • Journal Title: J.Clin.Endocrinol.Metab. 94 Pages: 1317-1323
  • Peer Reviewed
• [Journal Article] Rapid and reversible inhibition of aquaporin-4 by zinc (2009)
  • Author(s): Yukutake Y, Hirano Y, Suematsu M, Yasui M
  • Journal Title: Biochem. 48 Pages: 12059-12061
  • Peer Reviewed
• [Journal Article] Dynamic changes in amniotic tight junctions during pregnancy (2009)
  • Author(s): Kobayashi, K., Inai, T., Shibata, Y., Yasui, M
  • Journal Title: Placenta 30 Pages: 840-847
  • Peer Reviewed
• [Journal Article] pH regulated anion permeability of aquaporin-6 (2009)
  • Author(s): Yasui, M.
  • Journal Title: Handb.Exp.Pharmacol. 190 Pages: 299-308
  • Peer Reviewed
• [Journal Article] Aquaporin 6 binds calmodulin in a calcium-dependent manner (2009)
  • Author(s): Rabaud, N.E., Song, L., Wang, Y., Agre, P., Yasui, M., Carbrey, J.M.
  • Journal Title: Biochem.Biophys.Res.Commun. 383 Pages: 54-57
  • Peer Reviewed
• [Journal Article] Aquaporin-6 is expressed along the rat gastrointestinal tract and upregulated by feeding in the small intestine (2009)
  • Author(s): Laforenza, U., Gastaldi, G., Polimeni, M., Tritto, S., Tosco, M., Ventura, U., Scaffino, M.F., Yasui, M.
  • Journal Title: BMC Physiol. 9 Pages: 1-12
  • Peer Reviewed
• [Journal Article] Membrane potential dynamics of axons in cultured hippocampal neurons probed by second harmonic generation imaging (2009)
  • Author(s): Nuriya M, Yasui M.
  • Journal Title: Journal of Biomedical Optics (in press)
  • Peer Reviewed
• [Presentation] Water Biology:水分子ナノ動態から高次脳機能に迫る (2011)
  • Author(s): 安井 正人
  • Organizer: 第5 回トランスポーター研究会九州部会
  • Place of Presentation: ホテルJAL シティ 宮崎
  • Year and Date: 2011-09-17
• [Presentation] Water Biology:水分子ナノ動態から高次脳機能に迫る (2011)
  • Author(s): 安井正人
  • Organizer: 第5回トランスポーター研究会九州部会
  • Place of Presentation: ホテルJALシティ宮崎(宮崎)(招待講演)
  • Year and Date: 2011-09-17
• [Presentation] Water Biology:水分子ナノ動態から高次脳機能に迫る (2011)
  • Author(s): 安井 正人
  • Organizer: 創薬薬理フォーラム第19 回シンポジウム
  • Year and Date: 2011-09-13
• [Presentation] Water Biology:水分子ナノ動態から高次脳機能に迫る (2011)
  • Author(s): 安井正人
  • Organizer: 創薬薬理フォーラム第19回シンポジウム
  • Place of Presentation: 日本薬学会長井記念館(東京)(招待講演)
  • Year and Date: 2011-09-13
• [Presentation] Roles of aquaporins in water dynamics of the cells (2011)
  • Author(s): 安井正人
  • Organizer: International Conference "Water and Nanomedicine"
  • Place of Presentation: Academy of Sciences and Arts of Republic of Srpska Banja Luka (Bosnia and Herzegovina)(招待講演)
  • Year and Date: 2011-08-30
• [Presentation] Roles of aquaporins in water dynamics of the cells (2011)
  • Author(s): 安井 正人
  • Organizer: International Conference "Water and Nanomedicine"
  • Place of Presentation: Academy of Sciences and Arts of Republic of Srpska Banja Luka
  • Year and Date: 2011-08-16
• [Presentation] AQP と脳水腫 (2011)
  • Author(s): 安井 正人
  • Organizer: 北京大学医学部特別講演会
  • Place of Presentation: 北京大学医学部
  • Year and Date: 2011-08-16
• [Presentation] AQPと脳水腫 (2011)
  • Author(s): 安井正人
  • Organizer: 北京大学医学部特別講演会
  • Place of Presentation: 北京大学医学部(北京、中国)(招待講演)
  • Year and Date: 2011-08-16
• [Presentation] アクアポリンとドライシンドローム (2011)
  • Author(s): 安井 正人
  • Organizer: 日本ドライシンドローム学会設立記念講演会
  • Year and Date: 2011-03-04
• [Presentation] Roles of AQP4 in brain disorders, THE FIRST WORLD CONGRESS ON WATER CHANNEL PROTEINS (AQUAPORINS AND RELATIVES) (2011)
  • Author(s): 安井 正人
  • Organizer: CELEBRATING THE 25TH ANNIVERSARY OF THE DISCOVERY OF THE FIRST WATER CHANNEL PROTEIN(LATER CALLED AQUAPORIN 1)
  • Place of Presentation: CLUJ-NAPOCA, ROMANIA
• [Presentation] Perinatal dynamism of water balance and role of aquaporin (2011)
  • Author(s): 安井 正人
  • Organizer: 第11 回アジア小児腎臓学会学術集会, 第46 回日本小児腎臓病学会学術集会
  • Place of Presentation: 福岡国際会議場
• [Presentation] Perinatal dynamism of water balance and role of aquaporin (2011)
  • Author(s): 安井正人
  • Organizer: 第11回アジア小児腎臓学会学術集会第46回日本小児腎臓病学会学術集会
  • Place of Presentation: 福岡国際会議場(福岡)
• [Presentation] Roles of AQP4 in brain disorders (2011)
  • Author(s): 安井正人
  • Organizer: THE FIRST WORLD CONGRESS ON WATER CHANNEL PROTEINS (AQUAPORINS AND RELATIVES) CELEBRATING THE 25TH ANNIVERSARY OF THE DISCOVEEY OF THE FIRST WATER CHANNEL PEOTEIN (LATER CALLED AQUAPORIN 1)
  • Place of Presentation: CLUJ-NAPOCA, ROMANIA(招待講演)
• [Presentation] Integrated physiology in epithelial transport using non-linear optics and computer modeling (2010)
  • Author(s): 安井正人
  • Organizer: 第33回日本分子生物学会年会・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
  • Year and Date: 2010-12-08
• [Presentation] Aquaporin and Water Seen by Two Photon Microscopy (2009)
  • Author(s): 安井 正人
  • Organizer: WINPTech2009 Workshop on Information, Nano and Photonics Technology 2009
  • Place of Presentation: KOBE University Centennial Hall and Takikawa Memorial Hall, Kobe University
  • Year and Date: 2009-12-02
• [Presentation] Aquaporin and Water Seen by Two Photon Microscopy (2009)
  • Author(s): 安井正人
  • Organizer: WINPTech2009 Workshop on Information, Nano and Photonics Technology 2009
  • Place of Presentation: KOBE University Centennial Hall and Takikawa Memorial Hall, Kobe University, Kobe, Japan
  • Year and Date: 2009-12-02
• [Presentation] アクアポリン-4 の調節機構 (2009)
  • Author(s): 安井 正人
  • Organizer: 第39 回慶應ニューロサイエンス研究会, アクアポリン-4 と神経疾患-新たな病態メカニズムの展開と治療への戦略
  • Place of Presentation: 慶應義塾大学医学部 北里講堂
  • Year and Date: 2009-10-31
• [Presentation] アクアポリン-4の調節機構 (2009)
  • Author(s): 安井正人
  • Organizer: 第39回慶應ニューロサイエンス研究会『アクアポリン-4と神経疾患-新たな病態メカニズムの展開と治療への戦略』
  • Place of Presentation: 慶應義塾大学医学部 北里講堂
  • Year and Date: 2009-10-31
• [Presentation] Clinical relevance of water channel aquaporin (2009)
  • Author(s): 安井 正人
  • Organizer: The First International Meeting on Japan - China - Korea Traditional Medicine
  • Place of Presentation: 昭和薬科大学記念講堂
  • Year and Date: 2009-10-25
• [Presentation] Clinical relevance of water channel, aquaporin (2009)
  • Author(s): 安井正人
  • Organizer: The First International Meeting on Japan-China-Korea Traditional Medicine
  • Place of Presentation: 昭和薬科大学記念講堂(講義棟2F)
  • Year and Date: 2009-10-25
• [Presentation] Aquaporins in brain disorders (2009)
  • Author(s): 安井 正人
  • Organizer: 北京大学医学部
  • Place of Presentation: 北京大学
  • Year and Date: 2009-09-16
• [Presentation] Regulation, structure, and function of brain aquaporins (2009)
  • Author(s): 安井 正人
  • Organizer: The 22nd Biennial Joint Meeting of the International Society for Neurochemistry (ISN) and the Asian Pacific Society for Neurochemistry(APSN)
  • Place of Presentation: BEXCO, Busan, Korea,
  • Year and Date: 2009-08-24
• [Presentation] Regulation, structure, and function of brain aquaporins (2009)
  • Author(s): 安井正人
  • Organizer: The 22nd Biennial Joint Meeting of the International Society for Neurochemistry(ISN)and the Asian Pacific Society for Neurochemistry(APSN), Busan, Korea
  • Place of Presentation: BEXCO, Busan, Korea
  • Year and Date: 2009-08-24
• [Presentation] 水代謝の生理と病態に関する最新の話題ーアクアポリンの構造機能相関と分子標的創薬 (2009)
  • Author(s): 安井 正人
  • Organizer: 第44回日本小児腎臓病学会学術集会
  • Place of Presentation: 一橋記念講堂
  • Year and Date: 2009-06-26
• [Presentation] 水代謝の生理と病態に関する最新の話題-アクアポリンの構造機能相関と分子標的創薬 (2009)
  • Author(s): 安井正人
  • Organizer: 第44回日本小児腎臓病学会学術集会
  • Place of Presentation: 一橋記念講堂
  • Year and Date: 2009-06-26
• [Presentation] 中枢神経におけるアクアポリン-4(AQP4)の役割 (2009)
  • Author(s): 安井 正人
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2009-05-22
• [Remarks]
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• [Remarks] 薬理学教室HP
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