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MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric cardiac hypertrophy induced by a1-adrenergic receptors.

Authors: Ogata, Takehiro  Naito, Daisuke  Nakanishi, Naohiko  Hayashi, Yukiko K  Taniguchi, Takuya  Miyagawa, Kotaro  Hamaoka, Tetsuro  Maruyama, Naoki  Matoba, Satoaki  Ikeda, Koji  Yamada, Hiroyuki  Oh, Hidemasa  Ueyama, Tomomi 
Citation: Ogata T, etal., Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3811-6. doi: 10.1073/pnas.1315359111. Epub 2014 Feb 24.
Pubmed: (View Article at PubMed) PMID:24567387
DOI: Full-text: DOI:10.1073/pnas.1315359111

The actions of catecholamines on adrenergic receptors (ARs) induce sympathetic responses, and sustained activation of the sympathetic nervous system results in disrupted circulatory homeostasis. In cardiomyocytes, α1-ARs localize to flask-shaped membrane microdomains known as "caveolae." Caveolae require both caveolin and cavin proteins for their biogenesis and function. However, the functional roles and molecular interactions of caveolar components in cardiomyocytes are poorly understood. Here, we showed that muscle-restricted coiled-coil protein (MURC)/Cavin-4 regulated α1-AR-induced cardiomyocyte hypertrophy through enhancement of ERK1/2 activation in caveolae. MURC/Cavin-4 was expressed in the caveolae and T tubules of cardiomyocytes. MURC/Cavin-4 overexpression distended the caveolae, whereas MURC/Cavin-4 was not essential for their formation. MURC/Cavin-4 deficiency attenuated cardiac hypertrophy induced by α1-AR stimulation in the presence of caveolae. Interestingly, MURC/Cavin-4 bound to α1A- and α1B-ARs as well as ERK1/2 in caveolae, and spatiotemporally modulated MEK/ERK signaling in response to α1-AR stimulation. Thus, MURC/Cavin-4 facilitates ERK1/2 recruitment to caveolae and efficient α1-AR signaling mediated by caveolae in cardiomyocytes, which provides a unique insight into the molecular mechanisms underlying caveola-mediated signaling in cardiac hypertrophy.

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CRRD Object Information
CRRD ID: 12907554
Created: 2017-06-07
Species: All species
Last Modified: 2017-06-07
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.