Abstract
Healthy living throughout the lifespan requires continual growth and repair of cardiac, smooth, and skeletal muscle. To effectively maintain these processes muscle cells detect extracellular stress signals and efficiently transmit them to activate appropriate intracellular transcriptional programs. The striated muscle activator of Rho signaling (STARS) protein, also known as Myocyte Stress-1 (MS1) protein and Actin-binding Rho-activating protein (ABRA) is highly enriched in cardiac, skeletal, and smooth muscle. STARS binds actin, co-localizes to the sarcomere and is able to stabilize the actin cytoskeleton. By regulating actin polymerization, STARS also controls an intracellular signaling cascade that stimulates the serum response factor (SRF) transcriptional pathway; a pathway controlling genes involved in muscle cell proliferation, differentiation, and growth. Understanding the activation, transcriptional control and biological roles of STARS in cardiac, smooth, and skeletal muscle, will improve our understanding of physiological and pathophysiological muscle development and function.
Highlights
Healthy living throughout the lifespan requires continual growth and repair of cardiac, smooth, and skeletal muscle
LOCALIZATION AND ACTIVATION OF striated muscle activator of Rho signaling (STARS) In primary cardiomyocytes STARS locates to the sarcomere where it associates with the I-band, predominantly around the Z-disk and to a smaller extent in the M-line (Arai et al, 2002)
As the sarcomere plays a critical role in sensing biomechanical stress and activating signaling pathways in skeletal muscle, STARS could possibly act as a link between contractile function and intracellular signaling in muscle cells
Summary
(Wallace et al, 2011) and others (Arai et al, 2002) have observed its location in the nucleus. Gene expression of STARS is diminished in the heart of Mef2c null mouse embryos This suggests that Mef2c may be involved in the transcriptional regulation of STARS gene expression, at least in cardiac muscle (Kuwahara et al, 2007). Two conserved E-boxes have been identified within the proximal 1.5 kbp of the 5 upstream STARS promoter sequence (Ounzain et al, 2008). These two sites are required for recruiting MyoD and subsequently activating the STARS promoter during myogenic differentiation in C2C12 muscle cells. Recent work from our group identified a putative estrogen-related response element (ERRE) binding site on the STARS promoter (Wallace et al, 2011). Depletion of GATA4 allows the pathological up regulation of STARS (Ounzain et al, 2012)
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