Rho-associated protein kinase is involved in establishing the cardiomyocyte contractile phenotype

Степанова, О. В.; Чадин, А. В.; Masyutin, A. G.; Kulikova, T G; Gurin, Ya. V.; Sergeeva, I. A.; Shirinsky, Vladimir P.

doi:10.1134/s0006350910050167

Cited by 3 publications

(3 citation statements)

References 16 publications

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“…A previous report has shown at the light microscopy level, ROCK2 is distributed in intercalated discs (Stepanova et al, 2010). In this study, we found that at the electron microscopy level, ROCK2 is localized at the fascia adherens junctions and desmosomes of intercalated discs (Fig.…”

Section: Cell-cell Adhesion Sitessupporting

confidence: 63%

Distinct Distribution and Localization of Rho-kinase in Mouse Epithelial, Muscle and Neural Tissues

Iizuka

Kimura

Wang

et al. 2012

Cell Struct. Funct.

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ABSTRACT. The small GTP-binding protein Rho plays a crucial role in a wide variety of cellular functions through various effector proteins. Rho-kinase is a key effector protein of Rho, which is composed of two isoforms, ROCK1 and ROCK2. To clarify the site of action of ROCK1 and ROCK2, we performed immunofluorescence and immunoelectron microscopic analyses using isoform-specific antibodies in mouse tissues. In the large and small intestines, ROCK1 immunoreactivity was predominantly identified in epithelial cells, and ROCK2 immunoreactivity was negligible. In these epithelial cells, ROCK1 immunoreactivity was distributed on plasma membranes, while ROCK1 immunogold signals were localized at cell-cell contacts and cell adhesion sites, especially at the adherens junctions at the ultrastructural level. In the bladder epithelium, however, ROCK1 and ROCK2 signals were identified at intermediate filaments, and ROCK2 signals were also observed in nuclei. In the three types of muscular cells-smooth, cardiac, and skeletal muscle cells-ROCK1 and ROCK2 also showed differential distribution. ROCK1 signals were localized at actin filaments, plasma membranes, and vesicles near plasma membranes in smooth muscle cells; at the lysosomes in skeletal muscle cells; and were undetectable in cardiac muscle cells. ROCK2 signals were localized at actin filaments and centrosomes in smooth muscle cells, at intercalated discs in cardiac muscle cells, and at Z-discs and sarcoplasmic reticulum in skeletal muscle cells. In the brain, ROCK1 immunoreactivity was distributed in glia, whereas ROCK2 immunoreactivity was observed in neurons. These results indicate that the two isoforms of Rho-kinase distribute differentially to accomplish their specific functions.

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Section: Cell-cell Adhesion Sitessupporting

confidence: 63%

Distinct Distribution and Localization of Rho-kinase in Mouse Epithelial, Muscle and Neural Tissues

Iizuka

Kimura

Wang

et al. 2012

Cell Struct. Funct.

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“…This effect is associated with a depression of the maximal tension and a decrease in the Ca 2ϩ sensitivity (493). In addition, RhoA/Rho-kinase signaling has been proposed to participate in the maturation of myocardial contractile system through phosphorylation of its molecular targets in Z-discs and intercalated discs (464).…”

Section: Regulation Of Contractile Proteinsmentioning

confidence: 99%

Small G Proteins in the Cardiovascular System: Physiological and Pathological Aspects

Loirand

Sauzeau

Pacaud

2013

Physiological Reviews

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Small G proteins exist in eukaryotes from yeast to human and constitute the Ras superfamily comprising more than 100 members. This superfamily is structurally classified into five families: the Ras, Rho, Rab, Arf, and Ran families that control a wide variety of cell and biological functions through highly coordinated regulation processes. Increasing evidence has accumulated to identify small G proteins and their regulators as key players of the cardiovascular physiology that control a large panel of cardiac (heart rhythm, contraction, hypertrophy) and vascular functions (angiogenesis, vascular permeability, vasoconstriction). Indeed, basal Ras protein activity is required for homeostatic functions in physiological conditions, but sustained overactivation of Ras proteins or spatiotemporal dysregulation of Ras signaling pathways has pathological consequences in the cardiovascular system. The primary object of this review is to provide a comprehensive overview of the current progress in our understanding of the role of small G proteins and their regulators in cardiovascular physiology and pathologies.

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“…Other potential roles of ROCK in regulating contraction include participating in the maturation of the myocardial contractile system [101,102]; mediating the contraction-induced suppression of sarcoendoplasmic reticulum Ca 2+ -ATPase2a expression [103]. …”

Section: Rock In Cardiomyocytesmentioning

confidence: 99%

Rho Kinase As a Therapeutic Target in Cardiovascular Disease

Surma¹,

Wei²,

Shi³

2011

Future Cardiol.

166

138

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Rho kinase (ROCK) belongs to the AGC (PKA/PKG/PKC) family of serine/threonine kinases and is a major downstream effector of the small GTPase RhoA. ROCK plays central roles in the organization of the actin cytoskeleton and is involved in a wide range of fundamental cellular functions such as contraction, adhesion, migration, proliferation and gene expression. Two ROCK isoforms, ROCK1 a n d ROCK2, are assumed to be functionally redundant, based largely on the major common activators, the high degree of homology within the kinase domain and studies from overexpression with kinase constructs a n d chemical inhibitors (e.g., Y27632 a n d fasudil), which inhibit both ROCK1 and ROCK2. Extensive experimental a n d clinical studies support a critical role for the RhoA/ROCK pathway in the vascular bed in the pathogenesis of cardiovascular diseases, in which increased ROCK activity mediates vascular smooth muscle cell hypercontraction, endothelial dysfunction, inflammatory cell recruitment and vascular remodeling. Recent experimental studies, using ROCK inhibitors or genetic mouse models, indicate that the RhoA/ROCK pathway in myocardium contributes to cardiac remodeling induced by ischemic injury or persistent hypertrophic stress, thereby leading to cardiac decompensation and heart failure. This article, based on recent molecular, cellular and animal studies, focuses on the current understanding of ROCK signaling in cardiovascular diseases and in the pathogenesis of heart failure.

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Rho-associated protein kinase is involved in establishing the cardiomyocyte contractile phenotype

Cited by 3 publications

References 16 publications

Distinct Distribution and Localization of Rho-kinase in Mouse Epithelial, Muscle and Neural Tissues

Distinct Distribution and Localization of Rho-kinase in Mouse Epithelial, Muscle and Neural Tissues

Small G Proteins in the Cardiovascular System: Physiological and Pathological Aspects

Rho Kinase As a Therapeutic Target in Cardiovascular Disease

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