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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 (13 results) (of which Peer Reviewed: 13 results,  Acknowledgement Compliant: 4 results,  Open Access: 3 results) Remarks (3 results)

  • [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

      Molecular Cell

      Volume: 未定 Issue: 6 Pages: 1015-27

    • DOI

      10.1016/j.molcel.2015.04.008

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] IRBIT is novel determinant of catecholamine homeostasis through the TH phosphorylation by CaMKIIα2015

    • 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 U S A.

      Volume: 未定 Issue: 17 Pages: 5515-5520

    • DOI

      10.1073/pnas.1503310112

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Abolished InsP3R2 function inhibits sweat secretion in both humans and mice.2014

    • 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

      J Clin Invest.

      Volume: 124 Issue: 11 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 receptors.2014

    • 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 Issue: 38 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 eye.2014

    • 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 Issue: 6 Pages: e99205-e99205

    • DOI

      10.1371/journal.pone.0099205

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent dystonia by triggering tonic Purkinje cell firings in mice.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

      Front Neural Circuits.

      Volume: 7 Pages: 156-156

    • 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 Neurosci.

      Volume: 33 Issue: 30 Pages: 12186-96

    • DOI

      10.1523/jneurosci.0545-13.2013

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Striatum-specific expression of Cre recombinase using the Gpr88 promoter in mice.2013

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

      Transgenic Res.

      Volume: 22 Issue: 6 Pages: 1241-7

    • 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

      J Investigative Dermatology

      Volume: 132(9) Issue: 9 Pages: 2137-47

    • DOI

      10.1038/jid.2012.141

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cot Kinase Promotes Ca2+ Oscillation/Calcineurin-independent Osteoclastogenesis by Stabilizing NFATc1 Protein2012

    • Author(s)
      Kuroda Y
    • Journal Title

      Mol Cell Biology

      Volume: 32(14) Issue: 14 Pages: 2954-63

    • 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 mice2012

    • Author(s)
      Staats KA
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 429(3-4) Issue: 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 IP3RII and miRNA-133a regulates calcium signals and cardiac hypertrophy2012

    • Author(s)
      Drawnel FM
    • Journal Title

      J Cell Biology

      Volume: 199(5) Issue: 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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