2013 Fiscal Year Final Research Report
Elucidation of MURC-mediated mechanisms of caveolae function and transportsome formation in cardiomyocytes
Project/Area Number |
23591088
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
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Research Institution | Kyoto 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)
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Project Period (FY) |
2011 – 2013
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Keywords | 心肥大 / カベオラ / 心筋細胞 |
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.
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[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
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Journal Title
Proc Natl Acad Sci U S A
Volume: 111
Pages: 3811-3816
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[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
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Journal Title
Circ Cardiovasc Genet
Volume: 4
Pages: 349-358
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[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
Year and Date
20121100
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[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
Year and Date
20110800
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