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Journal of Biomedicine & Biotechnology 2010Calcium (Ca(2+)) signaling plays a key role in a wide range of physiological functions including control of cardiac and skeletal muscle performance. To assure a precise... (Review)
Review
Calcium (Ca(2+)) signaling plays a key role in a wide range of physiological functions including control of cardiac and skeletal muscle performance. To assure a precise coordination of both temporally and spatially transduction of intracellular Ca(2+) oscillations to downstream signaling networks and target operations, Ca(2+) cycling regulation in muscle tissue is conducted by a plethora of diverse molecules. Ca(2+) S100A1 is a member of the Ca(2+)-binding S100 protein family and represents the most abundant S100 isoform in cardiac and skeletal muscle. Early studies revealed distinct expression patterns of S100A1 in healthy and diseased cardiac tissue from animal models and humans. Further elaborate investigations uncovered S100A1 protein as a basic requirement for striated muscle Ca(2+) handling integrity. S100A1 is a critical regulator of cardiomyocyte Ca(2+) cycling and contractile performance. S100A1-mediated inotropy unfolds independent and on top of beta AR-stimulated contractility with unchanged beta AR downstream signaling. S100A1 has further been detected at different sites within the cardiac sarcomere indicating potential roles in myofilament function. More recently, a study reported a mitochondrial location of S100A1 in cardiomyocytes. Additionally, normalizing the level of S100A1 protein by means of viral cardiac gene transfer in animal heart failure models resulted in a disrupted progression towards cardiac failure and enhanced survival. This brief review is confined to the physiological and pathophysiological relevance of S100A1 in cardiac and skeletal muscle Ca(2+) handling with a particular focus on its potential as a molecular target for future therapeutic interventions.
Topics: Animals; Calcium; Humans; Mitochondria; Models, Biological; S100 Proteins; Sarcomeres; Sarcoplasmic Reticulum
PubMed: 20368797
DOI: 10.1155/2010/178614 -
Advances in Physiology Education Dec 2018One of the most iconic images in biology is the cross-striated appearance of a skeletal muscle fiber. The repeating band pattern shows that all of the sarcomeres are the...
One of the most iconic images in biology is the cross-striated appearance of a skeletal muscle fiber. The repeating band pattern shows that all of the sarcomeres are the same length. All of the A bands are the same length and are located in the middle of the sarcomeres. Furthermore, all of the myofibrils are transversely aligned across the muscle fiber. It has been known for 300 yr that skeletal muscle is striated, but only in the last 40 yr has a molecular understanding of the striations emerged. In the 1950s it was discovered that the extraction of myosin from myofibrils abolished the A bands, and the myofibrils were no longer striated. With the further extraction of actin, only the Z disks remained. Strangely, the sarcomere length did not change, and these "ghost" myofibrils still exhibited elastic behavior. The breakthrough came in the 1970s with the discovery of the gigantic protein titin. Titin, an elastic protein ~1 µm in length, runs from the Z disk to the middle of the A band and ensures that each sarcomere is the same length. Titin anchors the A band in the middle of the sarcomere and may determine thick-filament length and thus A-band length. In the 1970s it was proposed that the intermediate filament desmin, which surrounds the Z disks, connects adjacent myofibrils, resulting in the striated appearance of a skeletal muscle fiber.
Topics: Animals; Biomedical Research; Cytoskeleton; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Muscle, Skeletal; Muscle, Striated; Sarcomeres
PubMed: 30431326
DOI: 10.1152/advan.00152.2018 -
Advances in Experimental Medicine and... 2021Contraction of the striated muscle is fundamental for human existence. The action of voluntary skeletal muscle enables activities such as breathing, establishing body...
Contraction of the striated muscle is fundamental for human existence. The action of voluntary skeletal muscle enables activities such as breathing, establishing body posture, and diverse body movements. Additionally, highly precise motion empowers communication, artistic expression, and other activities that define everyday human life. The involuntary contraction of striated muscle is the core function of the heart and is essential for blood flow. Several ion channels are important in the transduction of action potentials to cytosolic Ca signals that enable muscle contraction; however, other ion channels are involved in the progression of muscle pathologies that can impair normal life or threaten it. This chapter describes types of selective and nonselective Ca permeable ion channels expressed in the striated muscle, their participation in different aspects of muscle excitation and contraction, and their relevance to the progression of some pathological states.
Topics: Calcium Channels; Humans; Muscle Contraction; Muscle, Skeletal; Myocardium; ORAI1 Protein
PubMed: 35138617
DOI: 10.1007/978-981-16-4254-8_11 -
Mechanical tension and spontaneous muscle twitching precede the formation of cross-striated muscle .Development (Cambridge, England) Apr 2017Muscle forces are produced by repeated stereotypical actomyosin units called sarcomeres. Sarcomeres are chained into linear myofibrils spanning the entire muscle fiber....
Muscle forces are produced by repeated stereotypical actomyosin units called sarcomeres. Sarcomeres are chained into linear myofibrils spanning the entire muscle fiber. In mammalian body muscles, myofibrils are aligned laterally, resulting in their typical cross-striated morphology. Despite this detailed textbook knowledge about the adult muscle structure, it is still unclear how cross-striated myofibrils are built Here, we investigate the morphogenesis of abdominal muscles and establish them as an model for cross-striated muscle development. By performing live imaging, we find that long immature myofibrils lacking a periodic actomyosin pattern are built simultaneously in the entire muscle fiber and then align laterally to give mature cross-striated myofibrils. Interestingly, laser micro-lesion experiments demonstrate that mechanical tension precedes the formation of the immature myofibrils. Moreover, these immature myofibrils do generate spontaneous Ca-dependent contractions , which, when chemically blocked, result in cross-striation defects. Taken together, these results suggest a myofibrillogenesis model in which mechanical tension and spontaneous muscle twitching synchronize the simultaneous self-organization of different sarcomeric protein complexes to build highly regular cross-striated myofibrils spanning the length of large muscle fibers.
Topics: Abdomen; Animals; Drosophila melanogaster; Lasers; Models, Biological; Morphogenesis; Muscle Contraction; Muscle Development; Muscle, Skeletal; Myofibrils; Optogenetics; Sarcomeres; Stress, Mechanical
PubMed: 28174246
DOI: 10.1242/dev.140723 -
Journal of Muscle Research and Cell... Feb 2015The contractile function of striated muscle cells is altered by oxidative/nitrosative stress, which can be observed under physiological conditions but also in diseases... (Review)
Review
The contractile function of striated muscle cells is altered by oxidative/nitrosative stress, which can be observed under physiological conditions but also in diseases like heart failure or muscular dystrophy. Oxidative stress causes oxidative modifications of myofilament proteins and can impair myocyte contractility. Recent evidence also suggests an important effect of oxidative stress on muscle elasticity and passive stiffness via modifications of the giant protein titin. In this review we provide a short overview of known oxidative modifications in thin and thick filament proteins and then discuss in more detail those oxidative stress-related modifications altering titin stiffness directly or indirectly. Direct modifications of titin include reversible disulfide bonding within the cardiac-specific N2-Bus domain, which increases titin stiffness, and reversible S-glutathionylation of cryptic cysteines in immunoglobulin-like domains, which only takes place after the domains have unfolded and which reduces titin stiffness in cardiac and skeletal muscle. Indirect effects of oxidative stress on titin can occur via reversible modifications of protein kinase signalling pathways (especially the NO-cGMP-PKG axis), which alter the phosphorylation level of certain disordered titin domains and thereby modulate titin stiffness. Oxidative stress also activates proteases such as matrix-metalloproteinase-2 and (indirectly via increasing the intracellular calcium level) calpain-1, both of which cleave titin to irreversibly reduce titin-based stiffness. Although some of these mechanisms require confirmation in the in vivo setting, there is evidence that oxidative stress-related modifications of titin are relevant in the context of biomarker design and represent potential targets for therapeutic intervention in some forms of muscle and heart disease.
Topics: Animals; Connectin; Elasticity; Glutathione; Humans; Muscle Contraction; Muscle, Skeletal; Oxidative Stress; Protein Processing, Post-Translational; Signal Transduction
PubMed: 25373878
DOI: 10.1007/s10974-014-9392-y -
Comprehensive Physiology Mar 2018Sarcomeres consist of highly ordered arrays of thick myosin and thin actin filaments along with accessory proteins. Thick filaments occupy the center of sarcomeres where... (Review)
Review
Sarcomeres consist of highly ordered arrays of thick myosin and thin actin filaments along with accessory proteins. Thick filaments occupy the center of sarcomeres where they partially overlap with thin filaments. The sliding of thick filaments past thin filaments is a highly regulated process that occurs in an ATP-dependent manner driving muscle contraction. In addition to myosin that makes up the backbone of the thick filament, four other proteins which are intimately bound to the thick filament, myosin binding protein-C, titin, myomesin, and obscurin play important structural and regulatory roles. Consistent with this, mutations in the respective genes have been associated with idiopathic and congenital forms of skeletal and cardiac myopathies. In this review, we aim to summarize our current knowledge on the molecular structure, subcellular localization, interacting partners, function, modulation via posttranslational modifications, and disease involvement of these five major proteins that comprise the thick filament of striated muscle cells. © 2018 American Physiological Society. Compr Physiol 8:631-709, 2018.
Topics: Animals; Humans; Muscle Contraction; Muscle Proteins; Muscle, Skeletal; Muscular Diseases; Mutation; Myofibrils; Myosins; Sarcomeres
PubMed: 29687901
DOI: 10.1002/cphy.c170023 -
The FEBS Journal Jul 2014Muscle lim protein (MLP) has emerged as a critical regulator of striated muscle physiology and pathophysiology. Mutations in cysteine and glycine-rich protein 3 (CSRP3),...
Muscle lim protein (MLP) has emerged as a critical regulator of striated muscle physiology and pathophysiology. Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, have been directly associated with human cardiomyopathies, whereas aberrant expression patterns are reported in human cardiac and skeletal muscle diseases. Increasing evidence suggests that MLP has an important role in both myogenic differentiation and myocyte cytoarchitecture, although the full spectrum of its intracellular roles has not been delineated. We report the discovery of an alternative splice variant of MLP, designated as MLP-b, showing distinct expression in neuromuscular disease and direct roles in actin dynamics and muscle differentiation. This novel isoform originates by alternative splicing of exons 3 and 4. At the protein level, it contains the N-terminus first half LIM domain of MLP and a unique sequence of 22 amino acids. Physiologically, it is expressed during early differentiation, whereas its overexpression reduces C2C12 differentiation and myotube formation. This may be mediated through its inhibition of MLP/cofilin-2-mediated F-actin dynamics. In differentiated striated muscles, MLP-b localizes to the sarcomeres and binds directly to Z-disc components, including α-actinin, T-cap and MLP. The findings of the present study unveil a novel player in muscle physiology and pathophysiology that is implicated in myogenesis as a negative regulator of myotube formation, as well as in differentiated striated muscles as a contributor to sarcomeric integrity.
Topics: Actins; Alternative Splicing; Amino Acid Sequence; Animals; Cell Differentiation; Cell Line; Humans; LIM Domain Proteins; Mice; Muscle Development; Muscle Proteins; Muscle, Skeletal; Muscle, Striated; Myoblasts; Neuromuscular Diseases; Protein Isoforms; Sequence Alignment
PubMed: 24860983
DOI: 10.1111/febs.12859 -
ELife Feb 2021Since the discovery of muscle in the 19th century, myosins as molecular motors have been extensively studied. However, in the last decade, a new functional super-relaxed...
Since the discovery of muscle in the 19th century, myosins as molecular motors have been extensively studied. However, in the last decade, a new functional super-relaxed (SRX) state of myosin has been discovered, which has a 10-fold slower ATP turnover rate than the already-known non-actin-bound, disordered relaxed (DRX) state. These two states are in dynamic equilibrium under resting muscle conditions and are thought to be significant contributors to adaptive thermogenesis in skeletal muscle and can act as a reserve pool that may be recruited when there is a sustained demand for increased cardiac muscle power. This report provides an evolutionary perspective of how striated muscle contraction is regulated by modulating this myosin DRX↔SRX state equilibrium. We further discuss this equilibrium with respect to different physiological and pathophysiological perturbations, including insults causing hypertrophic cardiomyopathy, and small-molecule effectors that modulate muscle contractility in diseased pathology.
Topics: Animals; Humans; Muscle, Skeletal; Myosins; Thermogenesis
PubMed: 33565963
DOI: 10.7554/eLife.63703 -
Advanced Drug Delivery Reviews Jul 2015microRNAs (miRs) are small non-protein-coding RNAs, able to post-transcriptionally regulate many genes and exert pleiotropic effects. Alteration of miR levels in tissues... (Review)
Review
microRNAs (miRs) are small non-protein-coding RNAs, able to post-transcriptionally regulate many genes and exert pleiotropic effects. Alteration of miR levels in tissues and in the circulation has been associated with various pathological and regenerative conditions. In this regard, tissue engineering of cardiac and skeletal muscles is a fascinating context for harnessing the complexity of miR-based circuitries and signals. In this review, we will focus on miR-driven regulation of cardiac and skeletal myogenic routes in homeostatic and challenging states. Furthermore, we will survey the intriguing perspective of exosomal and circulating miRs as novel paracrine players, potentially useful for current and future approaches of regenerative medicine for the striated muscles.
Topics: Animals; Epigenesis, Genetic; Exosomes; Heart; Heart Failure; Humans; MicroRNAs; Muscle, Skeletal; Regeneration; Tissue Engineering; Transcription Factors
PubMed: 25912658
DOI: 10.1016/j.addr.2015.04.011 -
The Journal of Clinical Investigation Feb 2020KBTBD13 is a protein expressed in striated muscle whose precise function is unknown. Work by de Winter et al. in this issue of the JCI provides evidence that KBTBD13...
KBTBD13 is a protein expressed in striated muscle whose precise function is unknown. Work by de Winter et al. in this issue of the JCI provides evidence that KBTBD13 localizes to the sarcomere and can directly bind actin. A mutation in KBTBD13 that is associated with nemaline myopathy alters the protein's effects on actin, apparently increasing thin-filament stiffness and ultimately depressing contractile force and relaxation rate. We discuss here the implications of this new sarcomeric protein, some alternate explanations for the effects of KBTBD13R408C, and the advantages of using computational models to interpret functional data from muscle.
Topics: Actins; Humans; Kinetics; Microfilament Proteins; Muscle Proteins; Muscle, Skeletal; Myopathies, Nemaline; Sarcomeres
PubMed: 31904591
DOI: 10.1172/JCI132954