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Redox-dependent regulation of an endoplasmic reticulum resident protein in neural function

Research Project

Project/Area Number 24500451
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

HISATSUNE Chihiro  独立行政法人理化学研究所, 脳科学総合研究センター, 研究員 (10321803)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords酸化還元 / 小胞体
Outline of Final Research Achievements

In this study, we found that ERp44, a factor involved in disulfide bond formation in the endoplasmic reticulum (ER), regulates angiotensin II. In mice, genetic loss of ERp44 destabilizes angiotensin II and causes hypotension. We found that ERp44 forms a mixed disulfide bond with ERAP1, an aminopeptidase that cleaves angiotensin II. ERp44 controls release of ERAP1 in a redox-dependent manner to control blood pressure. Additionally, we found that systemic inflammation triggers ERAP1 retention in the ER to inhibit hypotension. These results suggest that ERp44 redox-dependently regulates the intra- or extra-cellular localization of ERAP1, which contributes the control of serum angiotensin II level and blood pressure.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report

Research Products

(16 results)

All 2015 2014 2013 2012 Other

All Journal Article Remarks

  • [Journal Article] ERp44 Exerts Redox-Dependent Control of Blood Pressure at the ER2015

    • Author(s)
      Chihiro Hisatsune, Etsuko Ebisui, Masaya Usui, Naoko Ogawa, Akio Suzuki, Nobuko Mataga, Hiromi Takahashi-Iwanaga, and Katsuhiko Mikoshiba
    • Journal Title

      Mol Cell.

      Volume: 未定 Pages: 1015-27

    • DOI
      10.1016/j.molcel.2015.04.008
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] RBIT regulates CaMKIIα activity and contributes to catecholamine homeostasis through tyrosine hydroxylase phosphorylation.2015

    • Author(s)
      Katsuhiro Kawaai, Akihiro Mizutani, Hirotaka Shoji, Naoko Ogawa, Etsuko Ebisui, Yukiko Kuroda, Shigeharu Wakana, Tsuyoshi Miyakawa, Chihiro Hisatsune, Katsuhiko Mikoshiba
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 未定 Pages: 5515-20

    • DOI
      10.1073/pnas.1503310112
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Abolished InsP3R2 function inhibits sweat secretion in both humans and mice2014

    • Author(s)
      Klar J, Hisatsune C, Baig SM, Tariq M, Johansson AC, Rasool M, Malik NA, Ameur A, Sugiura K, Feuk L, Mikoshiba K, Dahl N.
    • Journal Title

      The Journal of Clinical Investigation

      Volume: 124 Pages: 4773-80

    • DOI
      10.1172/jci70720
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Aberrant calcium signaling by transglutaminase-mediated posttranslational modification of inositol 1,4,5-trisphosphate receptors2014

    • Author(s)
      Hamada K, Terauchi A, Nakamura K, Higo T, Nukina N, Matsumoto N, Hisatsune C, Nakamura T, Mikoshiba K.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 111 Pages: 3966-3975

    • DOI
      10.1073/pnas.1409730111
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye2014

    • Author(s)
      Inaba T, Hisatsune C, Sasaki Y, Ogawa Y, Ebisui E, Ogawa N, Matsui M, Takeuchi T, Mikoshiba K, Tsubota K.
    • Journal Title

      PLoS One

      Volume: 9

    • DOI
      10.1371/journal.pone.0099205
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 2-Aminoethyl diphenylborinate (2-APB) analogues: regulation of Ca2+ signaling.2013

    • Author(s)
      Hisatsune C, Miyamoto H, Hirono M, Yamaguchi N, Sugawara T, Ogawa N, Ebisui E, Ohshima T, Yamada M, Hensch TK, Hattori M, Mikoshiba K.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 7 Pages: 1-13

    • DOI
      10.3389/fncir.2013.00156
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Type 1 inositol trisphosphate receptor regulates cerebellar circuits by maintaining the spine morphology of purkinje cells in adult mice.2013

    • Author(s)
      Sugawara T, Hisatsune C, Le TD, Hashikawa T, Hirono M, Hattori M, Nagao S, Mikoshiba K.
    • Journal Title

      J Neuroscience

      Volume: 33 Pages: 12186-12196

    • DOI
      10.1523/jneurosci.0545-13.2013
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cre recombinase using the Gpr88 promoter in mice.2013

    • Author(s)
      Hisatsune C, Ogawa N, Mikoshiba K.
    • Journal Title

      Transgenic Res.

      Volume: 22 Pages: 1241-1247

    • DOI
      10.1007/s11248-013-9711-x
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of hair shedding by the type 3 IP3 receptor2012

    • Author(s)
      Sato-Miyaoka M
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 132(9) Pages: 2137-47

    • DOI
      10.1038/jid.2012.141
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cotkinase promotes Ca^<2+> oscillation/calcineurin-independent osteoclastogenesis by stabilizing NFATc1 protein2012

    • Author(s)
      Kuroda Y
    • Journal Title

      Mol Cell Biol

      Volume: 32(14) Pages: 2954-2963

    • DOI
      10.1128/mcb.05611-11
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neuronal overexpression of IP₃ receptor 2 is detrimental in mutant SOD1 mice.2012

    • Author(s)
      Staats KA
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 429(3-4) Pages: 210-213

    • DOI
      10.1016/j.bbrc.2012.10.094
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mutual antagonism between IP(3)RII and miRNA-133a regulates calcium signals and cardiac hypertrophy.2012

    • Author(s)
      Drawnel FM
    • Journal Title

      J Cell Biol.

      Volume: 199(5) Pages: 783-98

    • DOI
      10.1083/jcb.201111095
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Striatum-specific expression of Cre recombinase using the Gpr88 promoter in mice2012

    • Author(s)
      Chihiro Hisatsune, Naoko Ogawa, and Katsuhiko Mikoshiba
    • Journal Title

      Transgenic Research

      Volume: 印刷中

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Remarks] 無汗症患者の原因遺伝子を発見

    • URL
      http://www.riken.jp/pr/press/2014/20141021_1/
    • Related Report
      2014 Annual Research Report
  • [Remarks] 多動障害や社会行動の異常を抑える新しい分子機構を発見

    • URL
      http://www.riken.jp/pr/press/2015/20150414_1/
    • Related Report
      2014 Annual Research Report
  • [Remarks] 小胞体内腔タンパク質が血圧制御に重要な役割を果たす

    • URL
      http://www.riken.jp/pr/press/2015/20150508_1/
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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