Disease relevance of Sarcomeres

• MEK5 induced a form of hypertrophy in which cardiomyocytes acquired an elongated morphology and sarcomeres were assembled in a serial manner [1].
• These findings reveal a specific role for MEK5-ERK5 in the induction of eccentric cardiac hypertrophy and in transduction of cytokine signals that regulate serial sarcomere assembly [1].
• Reduced unloaded sarcomere shortening velocity and a shift to a slower myosin isoform in acute murine coxsackievirus myocarditis [2].
• The tumor with gli gene amplification lacked the usual histological features of alveolar or embryonal rhabdomyosarcoma; however, ultrastructural analysis of tumor cells established in culture revealed attenuated sarcomeres, resembling those found in primitive rhabdomyoblasts [3].
• Familial hypertrophic cardiomyopathy, central core disease, nemaline myopathy, and autosomal recessive limb-girdle muscular dystrophy have all been shown to involve mutations in proteins associated with the sarcomere [4].

Psychiatry related information on Sarcomeres

• The muscle biopsy findings in this patient suggest a new entity of congenital myopathy with clinical features of rigid spine, cardiomyopathy and restrictive respiratory insufficiency, characterized by peculiar abnormalities of ATPase staining in a mosaic pattern and, ultrastructurally, by zones of disorientation of the sarcomeres [5].

High impact information on Sarcomeres

• Unexpectedly, in addition to loss of Tnnt2 expression in sih mutant hearts, we observed a significant reduction in Tpma and Tnni3, and consequently, severe sarcomere defects [6].
• Cardiac troponin T is essential in sarcomere assembly and cardiac contractility [6].
• Because distinct mutations in sarcomere proteins cause either dilated or hypertrophic cardiomyopathy, the effects of mutant sarcomere proteins on muscle mechanics must trigger two different series of events that remodel the heart [7].
• Because alpha-tropomyosin and cardiac troponin T as well as beta myosin heavy chain mutations cause the same phenotype, we conclude that FHC is a disease of the sarcomere [8].
• Twelve mutants in the unc-52 II gene exhibit markedly retarded sarcomere construction and progressive paralysis [9].

Chemical compound and disease context of Sarcomeres

• Cardiac hypertrophy due to a chronic hemodynamic overload is accompanied by isoformic changes of two proteins of the thick filament of the sarcomere, myosin, and creatine phosphokinase [10].
• Maximum contraction amplitudes (sarcomere length change, micron) with isoproterenol before pertussis toxin were 0.144 +/- 0.011 (Y, n = 22 animals), 0.104 +/- 0.009 (A. 18) and 0.098 +/- 0.009 (S. 14), P < 0.01 by analysis of variance (ANOVA) [11].
• To determine whether changes in sarcomere length affect the inotropic response of the heart to angiotensin II (ANG II) differently in dilated and failing myocardium, papillary muscles were removed 2 days after infarction, and the effects of ANG II were studied at various muscle lengths [12].
• Furthermore, activation of protein kinase Cepsilon (PKCepsilon) was necessary for length recovery, as nonselective PKC inhibitors [staurosporine (5 micromol/L) and chelerythrine chloride (10 micromol/L)], and a replication-defective adenovirus (Adv) encoding a dominant-negative mutant of PKCepsilon prevented the restoration of sarcomere length [13].

Biological context of Sarcomeres

• The early appearance of titin in myofibrillogenesis suggests it may have a role in filament alignment during sarcomere assembly [14].
• Morphogenesis of the Caenorhabditis elegans embryo is driven by actin microfilaments in the epidermis and by sarcomeres in body wall muscles [15].
• The presence of a calmodulin-binding IQ motif, and a Rho guanine nucleotide exchange factor domain in the COOH-terminal region suggest that obscurin is involved in Ca(2+)/calmodulin, as well as G protein-coupled signal transduction in the sarcomere [16].
• During isometric contraction at sarcomere lengths 2.2-3.2 microm, the M3 x-ray reflection, associated with the repeat of myosin heads along the filaments, was resolved into two peaks [17].
• Phosphorylation may reinforce interactions between myosin rod domains, enhance thick filament connections to the central M-line of the sarcomere and/or stabilize thick filament interactions with proteins that contribute to fiber stiffness [18].

Anatomical context of Sarcomeres

• The individual units of the sarcomere, the basic contractile unit of myofibrils, include the thin, thick, titin, and nebulin filaments [19].
• We used single sarcomeres from which the Z-lines, structures which anchor the thin filaments in the sarcomere, had been completely removed by calcium-activated neutral protease (CANP) and trypsin, and measured both the sliding velocity of single actin filaments along myosin filaments and the ATPase activity during sliding [20].
• We hypothesize that ACTC mutations affecting sarcomere contraction lead to FHC and that mutations affecting force transmission from the sarcomere to the surrounding syncytium lead to IDC [21].
• Nebulin, a giant myofibrillar protein (600-800 kD) that is abundant (3%) in the sarcomere of a wide range of skeletal muscles, has been proposed as a component of a cytoskeletal matrix that coexists with actin and myosin filaments within the sarcomere [22].
• Using dominant-negative approaches in cardiac myocytes, both the titin Z1-Z2 domains and titin-cap are shown to be required for the structural integrity of sarcomeres, suggesting that their interaction is critical in titin filament-regulated sarcomeric assembly [23].

Associations of Sarcomeres with chemical compounds

• Titin and/or nebulin apparently provide axial continuity for the production of resting tension on stretch and also tend to keep the thick filaments centred within the sarcomere during force generation [24].
• Several hypertrophic agonists, such as angiotensin II, phenylephrine, and endothelin-1, have been shown to promote the sarcomere organization [25].
• Analysis of small areas of I-band and large areas, including several sarcomeres, suggested that chloride is anisotropically distributed, with some of it probably bound to myosin [26].
• The location of the threefold symmetric connection C4, relative to the thick filament of the adjacent sarcomere, is determined and its possible relationship to the C filament is considered [27].
• The localization of high-molecular-weight (80,000-200,000-daltons) proteins in the sarcomere of striated muscle has been studied by coordinated electron-microscopic and sodium dodecyl sulfate (SDS) gel electrophoretic analysis of native myofilaments and extracted and digested myofibrils [28].

Gene context of Sarcomeres

• First, we eliminated all actin or myosin in flight muscles to evaluate contributions of thick and thin filaments to sarcomere formation [29].
• ET-1 also induced a significant increase in atrial natriuretic factor mRNA expression as well as in the percentage of cells with highly organized sarcomeres, responses which were also blocked by expression of SEK-1(KR) [30].
• Absence of desmin filaments within the sarcomere does not interfere with primary muscle formation or regeneration [31].
• In intact muscles flightin is associated with the A band of the sarcomere, where evidence suggests it interacts with the myosin filaments [32].
• In the wild type, a constant ratio of the synthesis of the unc-54-coded myosin B to myosin A, about 2:1, is maintained during the larval stages in which the synthesis of both myosins increases exponentially and rapid sarcomere growth and addition ensues [33].

Analytical, diagnostic and therapeutic context of Sarcomeres

• Electron microscopy revealed a cardiomyocyte-like ultrastructure, including typical sarcomeres, a centrally positioned nucleus, and atrial granules [34].
• Immunofluorescence and immunoelectron microscopy studies revealed that myopalladin also colocalized with CARP in the central I-band of striated muscle sarcomeres [35].
• Cardiocyte function was assessed in terms of the ability to exclude trypan blue, to remain quiescent with relaxed sarcomeres containing I-bands, and to shorten in response to electrical stimulation [36].
• After 30 seconds of reperfusion the mean sarcomere length was significantly greater in the verapamil-treated hearts [37].
• We used the yeast two-hybrid assay to determine whether sAnk1 interacts with titin, a giant myofibrillar protein that organizes the sarcomere [38].

References