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2013 Fiscal Year Final Research Report

Molecular mechanism for targeting of NCX1 to basolateral membrane in renal epithelial cells

Research Project

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Project/Area Number 23590319
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionFukuoka University

Principal Investigator

IWAMOTO Takahiro  福岡大学, 医学部, 教授 (20300973)

Co-Investigator(Renkei-kenkyūsha) KITA Satomi  福岡大学, 医学部, 講師 (10461500)
ARAI Yuji  独立行政法人国立循環器病センター, バイオサイエンス部, 部長 (30202724)
Project Period (FY) 2011 – 2013
Keywordsイオン輸送体 / Ca2+シグナル / 腎上皮細胞 / 腎機能
Research Abstract

Na+/Ca2+ exchanger type 1 (NCX1) bidirectionally exchanges 3 Na+ with 1 Ca2+, depending on the electrochemical gradients across the plasma membrane. In renal tubule, NCX1 is localized to the basolateral membranes of distal convoluted tubule cells, and is considered to be involved in Ca2+ reabsorption. However, the molecular mechanisms for its membrane sorting remain to be elucidated. In the present study, we found that the intracellular domain of NCX1 interacts with the adaptor protein. Using GST pull-down assays, we further identified the binding motif in NCX1 molecule. We also found that the mutations in the binding motif of NCX1 affect its membrane sorting in epithelial MDCK cells, suggesting the interaction between NCX1 and the adaptor protein plays a key role in NCX1 basolateral sorting.

  • Research Products

    (48 results)

All 2014 2013 2012 2011 Other

All Journal Article (21 results) (of which Peer Reviewed: 20 results) Presentation (24 results) (of which Invited: 1 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Na^+/Ca^<2+> exchanger 1/2 double-heterozygote knockout mice display increased nitric oxide component and altered colonic motility2013

    • Author(s)
      Nishiyama K, Azuma YT, Kita S, Azuma N, Hayashi S, Nakajima H, Iwamoto T, Takeuchi T
    • Journal Title

      J Pharmacol Sci

      Volume: 123(3) Pages: 235-245

    • Peer Reviewed
  • [Journal Article] Dietary salt intake regulates WNK3-SPAK-NKCC1 phosphorylation cascade in mouse aorta through angiotensin II2013

    • Author(s)
      Zeniya M, Sohara E, Kita S, Iwamoto T, Susa K, Mori T, Oi K, Chiga M, Yang SS, Lin SH, Rai T, Sasaki S, Uchida S
    • Journal Title

      Hypertension

      Volume: 62(5) Pages: 872-878

    • DOI

      10.1161/HYPERTENSIONAHA.113.01543

    • Peer Reviewed
  • [Journal Article] Pretreatment of donor islets with the Na^+/Ca^<2+> exchanger inhibitor improves the efficiency of islet transplantation2013

    • Author(s)
      Mera T†, Itoh T†, Kita S†, (†co-first authors) Kodama S, Kojima D, Nishinakamura H, Okamoto K, Ohkura M, Nakai J, Iyoda T, Iwamoto T, Matsuda T, Baba A, Omori K, Ono J, Watarai H, Taniguchi M, Yasunami Y
    • Journal Title

      Am J Transplant

      Volume: 13(8) Pages: 2154-2160

    • DOI

      10.1111/ajt.12306

    • Peer Reviewed
  • [Journal Article] Structural basis for the counter-transport mechanism of a H^+/Ca^<2+> exchanger2013

    • Author(s)
      Nishizawa T, Kita S, Maturana AD, Furuya N, Hirata K, Kasuya G, Ogasawara S, Dohmae N, Iwamoto T, Ishitani R, Nureki O
    • Journal Title

      Science

      Volume: 341(6142) Pages: 168-172

    • DOI

      10.1126/science.1239002

    • Peer Reviewed
  • [Journal Article] Overactive bladder mediated by accelerated Ca^<2+> influx mode of Na^<+>/Ca^<2+> exchanger in smooth muscle2013

    • Author(s)
      Yamamura H, Cole WC, Kita S, Hotta S, Murata H, Suzuki Y, Ohya S, Iwamoto T, Imaizumi Y
    • Journal Title

      Am J Physiol Cell Physiol

      Volume: 305(3) Pages: C299-308

    • DOI

      10.1152/ajpcell.00065.2013

    • Peer Reviewed
  • [Journal Article] Quantitative analysis and cell distribution imaging of phosphoinositides2013

    • Author(s)
      Fujii M, Kita S, Gotoh Y, Horie I, Iwamoto T
    • Journal Title

      Med Bull Fukuoka Univ

      Volume: 40(3/4) Pages: 209-217

    • Peer Reviewed
  • [Journal Article] Ca^<2+>トランスポーターと循環器疾患2013

    • Author(s)
      喜多紗斗美, 藤井誠, 岩本隆宏
    • Journal Title

      医学のあゆみ

      Volume: 245(1) Pages: 5156

  • [Journal Article] 真核生物 CaCA結晶構造から哺乳類NCX の変異解析を検証する2013

    • Author(s)
      岩本隆宏, 喜多紗斗美
    • Journal Title

      日薬理誌

      Volume: 142(6) Pages: 318-319

    • Peer Reviewed
  • [Journal Article] 脂質シグナル研究のためのHPLC 分析技術:イノシトールリン脂質/イノシトールポリリン酸の分離と定量2013

    • Author(s)
      藤井誠, 喜多紗斗美, 平田雅人, 岩本隆宏
    • Journal Title

      日薬理誌

      Volume: 142(5) Pages: 236-240

    • Peer Reviewed
  • [Journal Article] Preferential involvement of Na⁺/Ca²⁺ exchanger type-1 in the brain damage caused by transient focal cerebral ischemia in mice2012

    • Author(s)
      Morimoto N, Kita S, Shimazawa M, Namimatsu H, Tsuruma K, Hayakawa K, Mishima K, Egashira N, Iyoda T, Horie I, Gotoh Y, Iwasaki K, Fujiwara M, Matsuda T, Baba A, Komuro I, Horie K, Takeda J, Iwamoto T, Hara H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 429(3-4) Pages: 186-190

    • DOI

      10.1016/j.bbrc.2012.10.114

    • Peer Reviewed
  • [Journal Article] Na^+/Ca^<2+> exchanger 2-heterozygote knockout mice display decreased acetylcholine release and altered colonic motility in vivo2012

    • Author(s)
      Azuma YT, Nishiyama K, Kita S, Komuro I, Nakajima H, Iwamoto T, Takeuchi T
    • Journal Title

      Neurogastroenterol Motil

      Volume: 24(12) Pages: e600-e610

    • DOI

      10.1111/nmo.12029

    • Peer Reviewed
  • [Journal Article] Effect of heterozygous deletion of WNK1 on the WNK-OSR1/SPAK-NCC/NKCC1/NKCC2 signal cascade in the kidney and blood vessels2012

    • Author(s)
      Susa K, Kita S, Iwamoto T, Yang SS, Lin SH, Ohta A, Sohara E, Rai T, Sasaki S, Alessi DR, Uchida S
    • Journal Title

      Clin Exp Nephrol

      Volume: 16(4) Pages: 530-538

    • Peer Reviewed
  • [Journal Article] Cellular and Physiological Functions of Phosphoinositide-Metabolizing Enzymes2012

    • Author(s)
      Fujii M, Kita S, Horie I, Gotoh Y, Iwamoto T
    • Journal Title

      Med Bull Fukuoka Univ

      Volume: 39(3/4) Pages: 281-287

    • Peer Reviewed
  • [Journal Article] The Roles of Aquaporins in Inflammatory and Ischemic Diseases2012

    • Author(s)
      Horie I, Gotoh Y, Kita S, Fujii M, Iwamoto T
    • Journal Title

      Med Bull Fukuoka Univ

      Volume: 39(3/4) Pages: 289-294

    • Peer Reviewed
  • [Journal Article] 結晶構造解析が解き明かすNa^+/Ca^<2+>交換輸送メカニズム2012

    • Author(s)
      岩本隆宏, 喜多紗斗美
    • Journal Title

      日薬理誌

      Volume: 140(5) Pages: 244

    • Peer Reviewed
  • [Journal Article] Na^+/Ca^<2+>交換輸送体をめぐるトランスポートソーム2012

    • Author(s)
      喜多紗斗美, 岩本隆宏
    • Journal Title

      日薬理誌

      Volume: 139(5) Pages: 61-65

    • Peer Reviewed
  • [Journal Article] TRIC-A channels in vascular smooth muscle contribute to blood pressure maintenance2011

    • Author(s)
      Yamazaki D, Tabara Y, Kita S, Hanada H, Komazaki S, Naitou D, Mishima A, Nishi M, Yamamura H, Yamamoto S, Kakizawa S, Miyachi H, Yamamoto S, Miyata T, Kawano Y, Kamide K, Ogihara T, Hata A, Umemura S, Soma M, Takahashi N, Imaizumi Y, Miki T, Iwamoto T, Takeshima H
    • Journal Title

      Cell Metab

      Volume: 14(2) Pages: 231-241

    • DOI

      10.1016/j.cmet.2011.05.011

    • Peer Reviewed
  • [Journal Article] Cilostazol suppresses angiotensin II-induced vasoconstriction via protein kinase A-mediated phosphorylation of the transient receptor potential canonical 6 channel2011

    • Author(s)
      Nishioka K, Nishida M, Ariyoshi M, Jian Z, Saiki S, Hirano M, Nakaya M, Sato Y, Kita S, Iwamoto T, Hirano K, Inoue R, Kurose H
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 31(10) Pages: 2278-2286

    • DOI

      10.1161/ATVBAHA.110.221010

    • Peer Reviewed
  • [Journal Article] Role of Na^+/Ca^<2+> exchanger type 1 (NCX1) in the angiogenesis induced by Lipo-PGE1 in murine hindlimb ischemia model2011

    • Author(s)
      Matsui Y, Kita S, Iyoda T, Katsuragi T, Komuro I, Iwamoto T, Ohjimi H
    • Journal Title

      Med Bull Fukuoka Univ

      Volume: 38(2) Pages: 77-84

    • Peer Reviewed
  • [Journal Article] New molecular mechanisms for cardiovascular disease2011

    • Author(s)
      Iwamoto T, Kawasaki H
    • Journal Title

      J Parmacol Sci

      Volume: 116(4) Pages: 321-322

    • Peer Reviewed
  • [Journal Article] New molecular mechanisms for cardiovascular disease: cardiac hypertrophy and cell-volume regulation2011

    • Author(s)
      Yamamoto S, Kita S, Iyoda T, Yamada T, Iwamoto T
    • Journal Title

      J Parmacol Sci

      Volume: 116(4) Pages: 343-349

    • Peer Reviewed
  • [Presentation] Na^+/Ca^<2+>交換体の構造・機能解析における最近の進歩2014

    • Author(s)
      岩本隆宏
    • Organizer
      第87回日本薬理学会年会サテライト(第23回細胞電気薬理研究会)
    • Place of Presentation
      仙台
    • Year and Date
      2014-03-18
    • Invited
  • [Presentation] 真核生物CaCA 結晶構造から哺乳類NCX 変異解析を検証する2013

    • Author(s)
      岩本隆宏
    • Organizer
      生理研研究会「心血管膜輸送分子の構造・機能・病態の統合的研究戦略」
    • Place of Presentation
      岡崎
    • Year and Date
      2013-11-27
  • [Presentation] 尿生成におけるCa^<2+>排泄におけるNa^+/Ca^<2+>交換輸送体の役割2013

    • Author(s)
      後藤雄輔, 喜多紗斗美, 藤井誠, 堀江一郎, 荒井勇二, 内田信一, 岩本隆宏
    • Organizer
      第66回日本薬理学会西南部会
    • Place of Presentation
      福岡
    • Year and Date
      2013-11-16
  • [Presentation] 血管平滑筋Na^+/Ca^<2+>交換体の機能制御と病態生理学的役割2013

    • Author(s)
      喜多紗斗美, 岩本隆宏
    • Organizer
      第55回日本平滑筋学会総会シンポジウム
    • Place of Presentation
      旭川
    • Year and Date
      2013-08-07
  • [Presentation] Involvement of TRPC3/6 channels in myogenic tone regulation and A1-adrenoceptor-mediated vasoconstriction of murine mesenteric arteries2013

    • Author(s)
      Kita S, Horie I, Arai Y, Iwamoto T
    • Organizer
      2nd HD physiology International Symposium
    • Place of Presentation
      Tokyo
    • Year and Date
      2013-06-29
  • [Presentation] 血管トーヌス制御におけるTRPC_S およびNCX1 を介するCa^<2+>動員機構2013

    • Author(s)
      喜多紗斗美, 岩本隆宏
    • Organizer
      第86回日本薬理学会年会シンポジウム
    • Place of Presentation
      福岡
    • Year and Date
      2013-03-22
  • [Presentation] カルシウム・プロトン交換輸送体の分子機構の構造基盤2013

    • Author(s)
      濡木理, 西澤知宏, 石谷隆一郎, 岩本隆宏
    • Organizer
      第86回日本薬理学会年会シンポジウム
    • Place of Presentation
      福岡
    • Year and Date
      2013-03-22
  • [Presentation] Na^+/Ca^<2+>交換輸送体のCa^<2+>依存性構造変化と膜局在化機構2013

    • Author(s)
      岩本隆宏
    • Organizer
      第86回日本薬理学会年会シンポジウム
    • Place of Presentation
      福岡
    • Year and Date
      2013-03-22
  • [Presentation] 膵β細胞のCa^<2+>調節機構におけるNa^+/Ca^<2+>交換体の役割2013

    • Author(s)
      喜多紗斗美, 岩本隆宏
    • Organizer
      第91回日本生理学会大会シンポジウム
    • Place of Presentation
      鹿児島
    • Year and Date
      2013-03-16
  • [Presentation] Preferential involvement of NCX1 in the brain damage caused by transient focal cerebral ischemia in mice2013

    • Author(s)
      Kita S, Morimoto N, Shimazawa M, Hara H, Iwamoto T
    • Organizer
      Biophysical Society 57th Annual Meeting
    • Place of Presentation
      Philadelphia
    • Year and Date
      2013-02-04
  • [Presentation] Augmentation of renal reperfusion injury in NCX2-Heterozygote knockout mice2013

    • Author(s)
      Kita S, Gotoh Y, Ogata M, Iwamoto T
    • Organizer
      Biophysical Society 57th Annual Meeting
    • Place of Presentation
      Philadelphia
    • Year and Date
      2013-02-04
  • [Presentation] マウス腸間膜細動脈の筋原性収縮および血圧調節おけるTRPC3 の役割2012

    • Author(s)
      喜多紗斗美, 堀江一郎, 岩本隆宏
    • Organizer
      平成24年度生理研研究会「心血管イオンチャネル・トランスポーター研究の新展開 –基礎研究と臨床研究の融合-」
    • Place of Presentation
      岡崎
    • Year and Date
      2012-11-24
  • [Presentation] Na^+/Ca^<2+>交換輸送体の細胞内Na^+依存性活性制御異常と心不全2012

    • Author(s)
      喜多紗斗美, 岩本隆宏
    • Organizer
      第7回トランスポーター研究会年会(シンポジウム)
    • Place of Presentation
      京都
    • Year and Date
      2012-06-10
  • [Presentation] Electrophysiological properties of YM-244769,a new and selective NCX blocker,in heart2012

    • Author(s)
      Watanabe Y, Kita S, Iwamoto T
    • Organizer
      Experimental Biology
    • Place of Presentation
      San Diego
    • Year and Date
      2012-04-25
  • [Presentation] Na^+/Ca^<2+> exchanger type-1 contributes to hypertension in pseudohypoaldosteronism type II and cushing's syndrome models2012

    • Author(s)
      Kita S, Uchida S, Komuro I, Iwamoto T
    • Organizer
      Biophysical society 56th Annual Meeting
    • Place of Presentation
      San Diego
    • Year and Date
      2012-02-29
  • [Presentation] Pharmacological properties of YM-244769, a specific Na^+/Ca^<2+> exchange inhibitor2012

    • Author(s)
      Kita S, Watanabe Y, Yamahita K, Yamada T, Yamamoto S, Kimura J, Iwamoto T
    • Organizer
      in cardiac myocytes. Biophysical society 56th Annual Meeting
    • Place of Presentation
      San Diego
    • Year and Date
      2012-02-27
  • [Presentation] Pharmacological profile of YM-244769, a specific NCX inhibitor, in cardiac myocytes2012

    • Author(s)
      Kita S, Watanabe Y, Yamahita K, Yamada T, Yamamoto S, Kimura J, Iwamoto T
    • Organizer
      第1回HDP 国際シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2012-01-21
  • [Presentation] Cardiac-specific overexpression of NCX1.1 mutant induces dilated cardiomyopathy in mice2012

    • Author(s)
      Kita S, Akahane S, Nakaya H, Morimoto S, Arai Y, Iwamoto T
    • Organizer
      第1回HDP 国際シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2012-01-20
  • [Presentation] NCX2 ヘテロ欠損マウスにおける腎機能異常および腎虚血易障害性2011

    • Author(s)
      後藤雄輔, 尾形政哉, 喜多紗斗美, 岩本隆宏
    • Organizer
      日光シンポジウム
    • Place of Presentation
      栃木
    • Year and Date
      2011-12-17
  • [Presentation] NCX1 輸送体の膜局在化シグナルとCa^<2+>輸送制御2011

    • Author(s)
      岩本隆宏
    • Organizer
      日光シンポジウム
    • Place of Presentation
      栃木
    • Year and Date
      2011-12-17
  • [Presentation] Na^+/Ca^<2+>交換体とアダプター蛋白質複合体因子の相互作用2011

    • Author(s)
      岩本隆宏, 伊豫田拓也, 堀江一郎, 喜多紗斗美
    • Organizer
      第23年度生理研研究会「心血管イオンチャネル・トランスポーター研究の新展開」
    • Place of Presentation
      岡崎
    • Year and Date
      2011-11-29
  • [Presentation] 新規特異的NCX 阻害薬YM-244769 の心筋Ca^<2+>オーバーロード抑制作用2011

    • Author(s)
      岩本隆宏, 喜多紗斗美, 渡邊康秀, 山下寛奈, 山田敏樹, 山本信太郎, 堀江一郎, 木村純子
    • Organizer
      第39回薬物活性シンポジウム
    • Place of Presentation
      福岡
    • Year and Date
      2011-11-21
  • [Presentation] ACTH 誘発性およびPHAII型高血圧におけるNCX1の役割2011

    • Author(s)
      喜多紗斗美, 堀江一郎, 内田信一, 小室一成, 岩本隆宏
    • Organizer
      第64回日本薬理学会西南部会
    • Place of Presentation
      福岡
    • Year and Date
      2011-11-20
  • [Presentation] NCX1 輸送体とアダプタータンパク質複合体因子の相互作用2011

    • Author(s)
      伊豫田拓也, 喜多紗斗美, 後藤雄輔, 岩本隆宏
    • Organizer
      第64回日本薬理学会西南部会
    • Place of Presentation
      福岡
    • Year and Date
      2011-11-20
  • [Book] 実践治療薬「食塩感受性高血圧とNa^+/Ca^<2+>交換体 : 食塩負荷から血管トーヌス亢進へのイオン機序」2012

    • Author(s)
      岩本隆宏, 喜多紗斗美
    • Total Pages
      171-181
    • Publisher
      株式会社金芳堂
  • [Book] 利尿薬 イラストレイテッド薬理学 [原著5 版] (編者:丸山敬・柳沢輝行)2012

    • Author(s)
      岩本隆宏
    • Total Pages
      331-346
    • Publisher
      丸善出版株式会社
  • [Remarks] ホームページ

    • URL

      http://www.med.fukuoka-u.ac.jp/pharmaco/jndex.html

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Published: 2015-07-16  

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