MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK pathway, induces cardiac dysfunction and conduction disturbance

Takehiro Ogata, Tomomi Ueyama, Koji Isodono, Masashi Tagawa, Naofumi Takehara, Tsuneaki Kawashima, Koichiro Harada, Tomosaburo Takahashi, Tetsuo Shioi, Hiroaki Matsubara, Hidemasa Oh

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

We identified a novel muscle-restricted putative coiled-coil protein, MURC, which is evolutionarily conserved from frog to human. MURC was localized to the cytoplasm with accumulation in the Z-line of the sarcomere in the murine adult heart. MURC mRNA expression in the heart increased during the developmental process from the embryonic stage to adulthood. In response to pressure overload, MURC mRNA expression increased in the hypertrophied heart. Using the yeast two-hybrid system, we identified the serum deprivation response (SDPR) protein, a phosphatidylserine-binding protein, as a MURC-binding protein. MURC induced activation of the RhoA/ROCK pathway, which modulated serum response factor-mediated atrial natriuretic peptide (ANP) expression and myofibrillar organization. SDPR augmented MURC-induced transactivation of the ANP promoter in cardiomyocytes, and RNA interference of SDPR attenuated the action of MURC on the ANP promoter. Transgenic mice expressing cardiac-specific MURC (Tg-MURC) exhibited cardiac contractile dysfunction and atrioventricular (AV) conduction disturbances with atrial chamber enlargement, reduced thickness of the ventricular wall, and interstitial fibrosis. Spontaneous episodes of atrial fibrillation and AV block were observed in Tg-MURC mice. These findings indicate that MURC modulates RhoA signaling and that MURC plays an important role in the development of cardiac dysfunction and conduction disturbance with increased vulnerability to atrial arrhythmias.

Original languageEnglish
Pages (from-to)3424-3436
Number of pages13
JournalMolecular and Cellular Biology
Volume28
Issue number10
DOIs
Publication statusPublished - May 2008
Externally publishedYes

Fingerprint

Atrial Natriuretic Factor
Muscles
Carrier Proteins
Serum
Serum Response Factor
Messenger RNA
Sarcomeres
Two-Hybrid System Techniques
Proteins
Atrioventricular Block
Phosphatidylserines
RNA Interference
Cardiac Myocytes
Anura
Atrial Fibrillation
Transgenic Mice
Transcriptional Activation
Cardiac Arrhythmias
Cytoplasm
Fibrosis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK pathway, induces cardiac dysfunction and conduction disturbance. / Ogata, Takehiro; Ueyama, Tomomi; Isodono, Koji; Tagawa, Masashi; Takehara, Naofumi; Kawashima, Tsuneaki; Harada, Koichiro; Takahashi, Tomosaburo; Shioi, Tetsuo; Matsubara, Hiroaki; Oh, Hidemasa.

In: Molecular and Cellular Biology, Vol. 28, No. 10, 05.2008, p. 3424-3436.

Research output: Contribution to journalArticle

Ogata, T, Ueyama, T, Isodono, K, Tagawa, M, Takehara, N, Kawashima, T, Harada, K, Takahashi, T, Shioi, T, Matsubara, H & Oh, H 2008, 'MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK pathway, induces cardiac dysfunction and conduction disturbance', Molecular and Cellular Biology, vol. 28, no. 10, pp. 3424-3436. https://doi.org/10.1128/MCB.02186-07
Ogata, Takehiro ; Ueyama, Tomomi ; Isodono, Koji ; Tagawa, Masashi ; Takehara, Naofumi ; Kawashima, Tsuneaki ; Harada, Koichiro ; Takahashi, Tomosaburo ; Shioi, Tetsuo ; Matsubara, Hiroaki ; Oh, Hidemasa. / MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK pathway, induces cardiac dysfunction and conduction disturbance. In: Molecular and Cellular Biology. 2008 ; Vol. 28, No. 10. pp. 3424-3436.
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AU - Kawashima, Tsuneaki

AU - Harada, Koichiro

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