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Elucidation of MURC-mediated mechanisms of caveolae function and transportsome formation in cardiomyocytes

Research Project

Project/Area Number 23591088
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

UEYAMA Tomomi  京都府立医科大学, 医学(系)研究科(研究院), 講師 (80379388)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords心肥大 / カベオラ / 心筋細胞 / MURC / cavin family
Research Abstract

Immunoelectron microscopy revealed that MURC was expressed in caveolae and T tubules in cardiomyocytes, and transmission electron microscopy showed that caveolae were retained in cardiomyocytes of MURC-knockout (KO) mice. Alpha-1 adrenergic receptor (AR) stimulation-induced ERK activation and cardiac hypertrophy were attenuated in MURC-KO mice compared with wild-type mice. Upon alpha-1-AR stimulation, both MURC and phosphorylated ERK were translocated from the plasma membrane to the perinuclear region in cardiomyocytes. Immunoprecipitation revealed that MURC was associated with phosphorylated and total ERK. These findings suggest that MURC is dispensable for caveolar formation in cardiomyocytes, and that MURC serves as an ERK-recruiting protein in the caveolae within cardiomyocytes. The recruiting function of MURC is necessary to elicit efficient signaling of the alpha-1-AR/ERK cascade in the caveolae in cardiac hypertrophy.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (46 results)

All 2014 2013 2012 2011 Other

All Journal Article (10 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (35 results) Remarks (1 results)

  • [Journal Article] MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced byα1-adrenergic receptors2014

    • Author(s)
      Ogata T, Naito D, Nakanishi N, Hayashi YK, Taniguchi T, Miyagawa K, Hamaoka T, Maruyama N, Matoba S, Ikeda K, Yamada H, Oh H, Ueyama T
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 111 Pages: 3811-3816

    • Related Report
      2013 Final Research Report
  • [Journal Article] MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by α1-adrenergic receptors.2014

    • Author(s)
      Ogata T, Naito D, Nakanishi N, Hayashi YK, Taniguchi T, Miyagawa K, Hamaoka T, Maruyama N, Matoba S, Ikeda K, Yamada H, Oh H, Ueyama T.
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 111 Issue: 10 Pages: 3811-3816

    • DOI

      10.1073/pnas.1315359111

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serglycin is a novel adipocytokine highly expressed in epicardial adipose tissue2013

    • Author(s)
      Imoto-Tsubakimoto H, Takahashi T, Ueyama T, Ogata T, Adachi A, Nakanishi N, Mizushima K, Naito Y, Matsubara H
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 423 Pages: 105-110

    • Related Report
      2013 Final Research Report
  • [Journal Article] PARM-1 promotes cardiomyogenic differentiation through regulating the BMP/Smad signaling pathway2013

    • Author(s)
      Nakanishi N, Takahashi T, Ogata T, Adachi A, Imoto-Tsubakimoto H, Ueyama T, Matsubara H
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 428 Pages: 500-505

    • Related Report
      2013 Final Research Report
  • [Journal Article] NFAT5 regulates the canonical Wnt pathway and is required for cardiomyogenic differentiation2012

    • Author(s)
      Adachi A, Takahashi T, Ogata T, Imoto-Tsubakimoto H, Nakanishi N, Ueyama T, Matsubara H
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 426 Pages: 317-323

    • Related Report
      2013 Final Research Report
  • [Journal Article] Molecular genetic and functional characterization implicate muscle-restricted coiled-coil gene (MURC) as a causal gene for familial dilated cardiomyopathy2011

    • Author(s)
      Rodriguez G, Ueyama T, Ogata T, Czernuszewicz G, Tan Y, Dorn GW 2nd, Bogaev R, Amano K, Oh H, Matsubara H, Willerson JT, Marian AJ
    • Journal Title

      Circ Cardiovasc Genet

      Volume: 4 Pages: 349-358

    • Related Report
      2013 Final Research Report
  • [Journal Article] Early Inflammatory Reactions in Atherosclerosis Are Induced by Tyrosine Kinase Proline-Rich Tyrosine Kinase/Reactive Oxygen Species-Mediated Release of Tumor Necrosis Factor-α and Subsequent Activation of the p21Cip1/Ets-1/p300 System.2011

    • Author(s)
      Katsume A, Okigaki M, Matsui A, Che J, Adachi Y, Kishita E, Yamaguchi S, Ikeda K, Ueyama T, Matoba S, Yamada H, Matsubara H.
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 31 Issue: 5 Pages: 1084-1092

    • DOI

      10.1161/atvbaha.110.221804

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Apoptosis regulator through modulating IAP expression (ARIA) controls the PI3K/Akt pathway in endothelial and endothelial progenitor cells2011

    • Author(s)
      Koide M, et al
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 108 Issue: 23 Pages: 9472-9477

    • DOI

      10.1073/pnas.1101296108

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular Genetic and Functional Characterization Implicate Muscle-Restricted Coiled-Coil Gene (MURC) as a Causal Gene for Familial Dilated Cardiomyopathy2011

    • Author(s)
      Rodriguez G, et al
    • Journal Title

      Circ Cardiovasc Genet

      Volume: 4 Issue: 4 Pages: 349-358

    • DOI

      10.1161/circgenetics.111.959866

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Loss of bcl-2 during the senescence exacerbates the impaired angiogenic functions in endothelial cells by deteriorating the mitochondrial redox state.2011

    • Author(s)
      Uraoka M, Ikeda K, Kurimoto-Nakano R, Nakagawa Y, Koide M, Akakabe Y, Kitamura Y, Ueyama T, Matoba S, Yamada H, Okigaki M, Matsubara H.
    • Journal Title

      Hypertension.

      Volume: 58 Issue: 2 Pages: 254-263

    • DOI

      10.1161/hypertensionaha.111.176701

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] MURC/Cavin-4 deficiency alleviates pulmonary arterial hypertension2014

    • Author(s)
      Nakanishi N, Ogata T, Maruyama N, Miyagawa K, Hamaoka T, Ueyama T
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京都
    • Related Report
      2013 Final Research Report
  • [Presentation] Genetic deletion of MURC/Cavin-4 aggravates abdominal aortic aneurysm2014

    • Author(s)
      Miyagawa K, Ogata T, Nakanishi N, Hamaoka T, Maruyama N, Ueyama T
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京都
    • Related Report
      2013 Final Research Report
  • [Presentation] SDPR/Cavin-2 prevents cardiomyocyte hypertrophy through the inhibition of Akt signaling2014

    • Author(s)
      Maruyama N, Ogata T, Nakanishi N, Miyagawa K, Hamaoka T, Ueyama T
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京都
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC/Cavin-4 modulates caveolin-3 function and regulates cardiac function2014

    • Author(s)
      Hamaoka T, Naito D, Ogata T, Nakanishi N, Miyagawa K, Maruyama N, T Shirayama, Ueyama T
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京都
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC/cavin-4 modulates caveolin-3 function and regulates cardiac function.2014

    • Author(s)
      Hamaoka T, Naito D, Ogata T, Nakanishi N, Miyagawa K, Maruyama N, T Shirayama, Ueyama T.
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] Deficiency of MURC/Cavin-4 alleviates pulmonary arterial hypertension2013

    • Author(s)
      Nakanishi N, Ogata T, Miyagawa K, Hamaoka T, Maruyama N, Ueyama T
    • Organizer
      American Heart Association Scientific Session 2013
    • Place of Presentation
      Dallas, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC promotes recruitment of ERK1/2 to caveolae of the plasma membrane and concentric cardiac hypertrophy induced byα1-adrenergic stimulation2013

    • Author(s)
      Ogata T, Nakanishi N, Miyagawa K, Hamaoka T, Maruyama N, Ueyama T
    • Organizer
      American Heart Association Scientific Session 2013
    • Place of Presentation
      Dallas, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Genetic deletion of MURC/cavin-4 aggravates abdominal aortic aneurysm2013

    • Author(s)
      Miyagawa K, Ogata T, Nakanishi N, Hamaoka T, Maruyama N, Ueyama T
    • Organizer
      American Heart Association Scientific Session 2013
    • Place of Presentation
      Dallas, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC/Cavin-4 negatively regulates protective effects of caveolin-3 in cardiac function2013

    • Author(s)
      Naito D, Ueyama T, Kobara M, Amano K, Ogata T, Taniguchi T, Nakanishi N, Miyagawa K, Matsubara H
    • Organizer
      第77回日本循環器学会学術集会
    • Place of Presentation
      神奈川県
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC/Cavin-4, a muscle-specific caveolae-related protein, mediates the development of pulmonary arterial hypertension though enhanced Gα13/p115RhoGEF/RhoA signaling2013

    • Author(s)
      Nakanishi N, Ogata T, Miyagawa K, Naito D, Taniguchi T, Ueyama T, Matsubara H
    • Organizer
      第77回日本循環器学会学術集会
    • Place of Presentation
      神奈川県
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC/Cavin-4, a Muscle-restricted caveolar scaffolding protein for activated ERK, regulates cardiac hypertrophy induced byα1-adrenergic agonist2013

    • Author(s)
      Ogata T, Ueyama T, Naito D, Nakanishi N, Taniguchi T, Miyagawa K, Hamaoka T, Matsubara H
    • Organizer
      第77回日本循環器学会学術集会
    • Place of Presentation
      神奈川県
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC regulates Rho/ROCK signaling in vascular smooth muscle cells and mediates the development of pulmonary arterial hypertension2013

    • Author(s)
      Nakanishi N, Ogata T, Miyagawa K, Hamaoka T, Maruyama N, Ueyama T
    • Organizer
      第21回日本血管生物学会学術集会
    • Place of Presentation
      大阪府
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC/Cavin-4 has a protective role in the progression of abdominal aortic aneurysm2013

    • Author(s)
      Miyagawa K, Ogata T, Nakanishi N, Hamaoka T, Maruyama N, Ueyama T
    • Organizer
      第21回日本血管生物学会学術集会
    • Place of Presentation
      大阪府
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC Promotes Recruitment of Erk1/2 to Caveolae of The Plasma Membrane and Concentric Cardiac Hypertrophy Induced by α1-adrenergic Stimulation.2013

    • Author(s)
      Ogata T, Nakanishi N, Miyagawa K, Hamaoka T, Maruyama N, Ueyama.
    • Organizer
      American Heart Association Scientific Sessions 2013
    • Place of Presentation
      Dallas, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] MURC/Cavin-4 Negatively Regulates Protective Effects of Caveolin-3 in Cardiac Function.2013

    • Author(s)
      Naito D, et al.
    • Organizer
      第77回日本循環器学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] MURC/Cavin-4, a Muscle-restricted Caveolar Scaffolding Protein for Activated ERK, Regulates Cardiac Hypertrophy Induced by α1-Adrenergic Agonist.2013

    • Author(s)
      Ogata T, et al.
    • Organizer
      第77回日本循環器学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] MURC/Cavin-4, a muscle-specific caveolae-related protein, mediates the development of pulmonary arterial hypertension through enhanced Gα13/p115RhoGEF/RhoA signaling2012

    • Author(s)
      Nakanishi N, Ogata T, Miyagawa K, Naito D, Taniguchi T, Ueyama T, Matsubara H
    • Organizer
      American Heart Association Scientific Session 2012
    • Place of Presentation
      Las Vegas, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC/Cavin-4 functions as a negative regulator of caveolin-3 in the development of heart failure2012

    • Author(s)
      Naito D, Ueyama T, Kobara M, Amano K, Ogata T, Taniguchi T, Nakanishi N, Miyagawa K, Matsubara H
    • Organizer
      American Heart Association Scientific Session 2012
    • Place of Presentation
      Las Vegas, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC/Cavin-4, a new caveolar scaffolding protein for activated ERK, regulates cardiac hypertrophy induced byα1-adrenergic agonist2012

    • Author(s)
      Ogata T, Ueyama T, Taniguchi T, Naito D, Nakanishi N, Miyagawa K, Hamaoka T, Matsubara H
    • Organizer
      American Heart Association Scientific Session 2012
    • Place of Presentation
      Las Vegas, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Caveolae-related genes in heart failure and arrhythmia2012

    • Author(s)
      Ueyama T, Ogata T, Amano K, Matsubara H
    • Organizer
      第76回日本循環器学会学術集会
    • Place of Presentation
      福岡県
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC functions as a caveolar scaffold protein for Rho signaling that regulates proliferation and migration of vascular smooth muscle cells2012

    • Author(s)
      Nakanishi N, Ogata T, Miyagawa K, Naito D, Taniguchi T, Amano K, Ueyama T, Matsubara H
    • Organizer
      第76回日本循環器学会学術集会
    • Place of Presentation
      福岡県
    • Related Report
      2013 Final Research Report
  • [Presentation] Loss of MURC targeting to caveolae causes progressive cardiac dysfunction and intraventricular conduction delay2012

    • Author(s)
      Naito D, Amano K, Ogata T, Taniguchi T, Nakanishi N, Miyagawa K, Ueyama T, Matsubara H
    • Organizer
      第76回日本循環器学会学術集会
    • Place of Presentation
      福岡県
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC/Cavin-4 is a new caveolar scaffolding protein for phosphorylated ERK and regulatesα1-adrenergic agonist-induced cardiomyocyte hypertrophy2012

    • Author(s)
      Ogata T, Ueyama T, Naito D, Taniguchi T, Nakanishi N, Miyagawa K, Amano K, Matsubara H
    • Organizer
      第49回日本臨床分子医学会学術集会
    • Place of Presentation
      京都府
    • Related Report
      2013 Final Research Report
  • [Presentation] 筋特異的カベオラ蛋白MURCはCaveolin-1とGα13-GTPの結合を競合阻害し、Rho/ROCK pathwayを介した肺血管平滑筋細胞の増殖能・遊走能を亢進させる2012

    • Author(s)
      中西直彦、小形岳寛、宮川浩太郎、内藤大督、谷口琢也、沢田尚久、上山知己、松原弘明
    • Organizer
      第1回日本肺循環学会学術集会
    • Place of Presentation
      東京都
    • Related Report
      2013 Final Research Report
  • [Presentation] Impairment of MURC/Cavin-4 localization to caveolae causes progressive cardiac dysfunction and intraventricular conduction delay2012

    • Author(s)
      Naito D, Amano K, Ogata T, Taniguchi T, Nakanishi N, Miyagawa K, Ueyama T, Matsubara H
    • Organizer
      第29回国際心臓研究学会(ISHR)日本部会総会
    • Place of Presentation
      福岡県
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC/cavin-4 Functions as a Negative Regulator of Caveolin-3 in The Development of Heart Failure.2012

    • Author(s)
      Naito D, et al.
    • Organizer
      American Heart Association Scientific Sessions 2012
    • Place of Presentation
      Los Angeles, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] MURC/Cavin-4, a New Caveolar Scaffolding Protein for Activated ERK, Regulates Cardiac Hypertrophy Induced by α1-Adrenergic Agonist.2012

    • Author(s)
      Ogata T, et al.
    • Organizer
      American Heart Association Scientific Sessions 2012
    • Place of Presentation
      Los Angeles, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] MURC regulates proliferation of vascular smooth muscle cells through the Rho/ROCK pathway2011

    • Author(s)
      Nakanishi N, Ogata T, Miyagawa K, Naito D, Taniguchi T, Amano K, Ueyama T, Matsubara H
    • Organizer
      第75回日本循環器学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC, muscle-restricted coiled-coil protein, is a component of the caveolin-cavin complex and regulates caveolae morphology in cardiomyocytes2011

    • Author(s)
      Naito D, Amano K, Ogata T, Taniguchi T, Nakanishi N, Miyagawa K, Hayashi YK, Morimoto T, Ueyama T, Matsubara H
    • Organizer
      第75回日本循環器学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] NFAT5 is essential for mesodermal and cardiomyogenic differentiation through regulating the canonical Wnt pathway2011

    • Author(s)
      Adachi A, Takahashi T, Imoto H, Nakanishi N, Kangawa H, Ueyama T, Matsubara H
    • Organizer
      第75回日本循環器学会総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC/Cavin-4のRho/ROCK pathwayを介した血管平滑筋機能制御メカニズムの検討2011

    • Author(s)
      中西直彦,小形岳寛,宮川浩太郎,内藤大督,谷口琢也,天野克也,上山知己,松原弘明
    • Organizer
      第34回日本高血圧学会総会
    • Place of Presentation
      宇都宮
    • Related Report
      2013 Final Research Report
  • [Presentation] MURC regulates proliferation of vascular smooth muscle cells through the Rho/ROCK pathway.2011

    • Author(s)
      Nakanishi N, Ogata T, Miyagawa K, Naito D, Taniguchi T, Amano K, Ueyama T, Matsubara H.
    • Organizer
      第75回日本循環器学会総会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] MURC, muscle-restricted coiled-coil protein, is a component of the caveolin-cavin complex and regulates caveolae morphology in cardiomyocytes.2011

    • Author(s)
      Naito D, Amano K, Ogata T, Taniguchi T, Nakanishi N, Miyagawa K, Hayashi YK, Morimoto T, Ueyama T, Matsubara H.
    • Organizer
      第75回日本循環器学会総会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] NFAT5 is essential for mesodermal and cardiomyogenic differentiation through regulating the canonical Wnt pathway.2011

    • Author(s)
      Adachi A, Takahashi T, Imoto H, Nakanishi N, Kangawa H, Ueyama T, Matsubara H.
    • Organizer
      第75回日本循環器学会総会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Presentation] MURC/Cavin-4のRho/ROCK pathwayを介した血管平滑筋機能制御メカニズムの検討.2011

    • Author(s)
      中西直彦,小形岳寛,宮川浩太郎,内藤大督,谷口琢也,天野克也,上山知己,松原弘明.
    • Organizer
      第34回日本高血圧学会総会
    • Place of Presentation
      宇都宮
    • Related Report
      2011 Research-status Report
  • [Remarks] 循環器・腎臓内科ホームページ

    • URL

      http://www.f.kpu-m.ac.jp/k/med2/index.html

    • Related Report
      2013 Annual Research Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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