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Cells & Development Dec 2021Muscles generate forces for animal locomotion. The contractile apparatus of muscles is the sarcomere, a highly regular array of large actin and myosin filaments linked... (Review)
Review
Muscles generate forces for animal locomotion. The contractile apparatus of muscles is the sarcomere, a highly regular array of large actin and myosin filaments linked by gigantic titin springs. During muscle development many sarcomeres assemble in series into long periodic myofibrils that mechanically connect the attached skeleton elements. Thus, ATP-driven myosin forces can power movement of the skeleton. Here we review muscle and myofibril morphogenesis, with a particular focus on their mechanobiology. We describe recent progress on the molecular structure of sarcomeres and their mechanical connections to the skeleton. We discuss current models predicting how tension coordinates the assembly of key sarcomeric components to periodic myofibrils that then further mature during development. This requires transcriptional feedback mechanisms that may help to coordinate myofibril assembly and maturation states with the transcriptional program. To fuel the varying energy demands of muscles we also discuss the close mechanical interactions of myofibrils with mitochondria and nuclei to optimally support powerful or enduring muscle fibers.
Topics: Animals; Biophysics; Morphogenesis; Myofibrils; Myosins; Sarcomeres
PubMed: 34863916
DOI: 10.1016/j.cdev.2021.203760 -
Cytoskeleton (Hoboken, N.J.) Oct 2020De novo assembly of myofibrils in vertebrate cross-striated muscles progresses in three distinct steps, first from a minisarcomeric alignment of several nonmuscle and...
De novo assembly of myofibrils in vertebrate cross-striated muscles progresses in three distinct steps, first from a minisarcomeric alignment of several nonmuscle and muscle proteins in premyofibrils, followed by insertions of additional proteins and increased organization in nascent myofibrils, ending with mature contractile myofibrils. In a search for controls of the process of myofibril assembly, we discovered that the transition from nascent to mature myofibrils could be halted by inhibitors of three distinct functions of the ubiquitin proteasome system (UPS). First, inhibition of pathway to E3 Cullin ligases that ubiquitinate proteins led to an arrest of myofibrillogenesis at the nascent myofibril stage. Second, inhibition of p97 protein extractions of ubiquitinated proteins led to a similar arrest of myofibrillogenesis at the nascent myofibril stage. Third, inhibitors of proteolytic action by proteasomes also blocked nascent myofibrils from transitioning to mature myofibrils. In contrast, inhibitors of autophagy or lysosomes did not affect myofibrillogenesis. To probe for differences in the effects of UPS inhibitors during myofibrillogenesis, we analyzed by fluorescence recovery after photobleaching the exchange rates of two selected sarcomeric proteins (muscle myosin II heavy chains and light chains). In the presence of p97 and proteasomal inhibitors, the dynamics of each of these two myosin proteins decreased in the nascent myofibril stage, but were unaffected in the mature myofibril stage. The increased stability of myofibrils occurring in the transition from nascent to mature myofibril assembly indicates the importance of dynamics and selective destruction in the muscle myosin II proteins for the remodeling of nascent to mature myofibrils.
Topics: Animals; Muscle, Skeletal; Myofibrils; Proteasome Endopeptidase Complex; Quail; Ubiquitin
PubMed: 33124174
DOI: 10.1002/cm.21641 -
Trends in Cell Biology Sep 2000One of the most fascinating examples of cytoskeletal assembly is the myofibril, the contractile structure of striated (i.e. skeletal and cardiac) muscle. Myofibrils are... (Review)
Review
One of the most fascinating examples of cytoskeletal assembly is the myofibril, the contractile structure of striated (i.e. skeletal and cardiac) muscle. Myofibrils are composed of repeating contractile units known as sarcomeres, perhaps the most highly ordered macromolecular structures in eukaryotic cells. When skeletal and cardiac muscle cells differentiate, thousands of structural and regulatory molecules assemble into the semicrystalline sarcomeric contractile units. As a consequence of this precise assembly, many different classes of proteins function together to convert the molecular interactions of actin and myosin efficiently into the macroscopic movements of contractile activity.
Topics: Animals; Humans; Muscle, Skeletal; Myocardium; Myofibrils
PubMed: 10932092
DOI: 10.1016/s0962-8924(00)01793-1 -
Frontiers in Bioscience (Landmark... Jan 2012Cardiomyocytes are coordinated by linking together at their ends through the intercalated disc. The intercalated disc with its complex folded membrane, encompasses many... (Review)
Review
Cardiomyocytes are coordinated by linking together at their ends through the intercalated disc. The intercalated disc with its complex folded membrane, encompasses many structural and signalling functions and is thought to play a role in cell growth and sarcomere addition. Its relationship to the contractile myofibrils is central to myocyte function. The myofibrils continue their ordered sarcomeric structure up to the edge of the intercalated disc where there is no terminal Z-disc but, instead a transitional junction. Thin actin-containing filaments from the final half sarcomere extend beyond their normal length through the transitional junction to the folded intercalated disc membrane where tension is transmitted. The peaks of the membrane folds also occur at the transitional level. They are spectrin rich and associated with sarcoplasmic reticulum vesicles. A subset of Z-disc proteins including titin, alpha-actinin and ZASP/cypher/oracle are found in the transitional region while others such as telethonin and FATZ/calsarcin/myozenin are absent. The presence of titin enables ordered sarcomeres to be maintained independently of changes in the amplitude of the membrane folds. The transitional junction is therefore poised to act as a site for a new Z-disc/SR/T-tubule complex and sarcomere addition. The evidence for this is reviewed.
Topics: Animals; Cell Membrane; Mice; Microscopy, Electron; Myocardium; Myofibrils
PubMed: 22201789
DOI: 10.2741/3972 -
Nature Communications Apr 2021Complex animals build specialised muscles to match specific biomechanical and energetic needs. Hence, composition and architecture of sarcomeres and mitochondria are...
Complex animals build specialised muscles to match specific biomechanical and energetic needs. Hence, composition and architecture of sarcomeres and mitochondria are muscle type specific. However, mechanisms coordinating mitochondria with sarcomere morphogenesis are elusive. Here we use Drosophila muscles to demonstrate that myofibril and mitochondria morphogenesis are intimately linked. In flight muscles, the muscle selector spalt instructs mitochondria to intercalate between myofibrils, which in turn mechanically constrain mitochondria into elongated shapes. Conversely in cross-striated leg muscles, mitochondria networks surround myofibril bundles, contacting myofibrils only with thin extensions. To investigate the mechanism causing these differences, we manipulated mitochondrial dynamics and found that increased mitochondrial fusion during myofibril assembly prevents mitochondrial intercalation in flight muscles. Strikingly, this causes the expression of cross-striated muscle specific sarcomeric proteins. Consequently, flight muscle myofibrils convert towards a partially cross-striated architecture. Together, these data suggest a biomechanical feedback mechanism downstream of spalt synchronizing mitochondria with myofibril morphogenesis.
Topics: Animals; Biomechanical Phenomena; Drosophila; Drosophila Proteins; Drosophila melanogaster; Feedback; Flight, Animal; Male; Mechanical Phenomena; Mitochondria; Morphogenesis; Muscle Development; Muscle, Skeletal; Myofibrils; Myogenic Regulatory Factors; Sarcomeres; Transcription Factors
PubMed: 33828099
DOI: 10.1038/s41467-021-22058-7 -
Beitrage Zur Gerichtlichen Medizin 1990Mechanical trauma to the heart induces a rhythmical transverse banding of adjacent myocytes. This finding is due to hypercontraction (true contraction bands) and it is... (Review)
Review
Mechanical trauma to the heart induces a rhythmical transverse banding of adjacent myocytes. This finding is due to hypercontraction (true contraction bands) and it is different from the cross band type myofibrillar degeneration (MFD) which is characterized by disseminated foci of irregular transverse banding. This latter type is mainly found after temporary myocardial ischemia, in cases of reanimation using catecholamines and defibrillation as well as in severe brain trauma. Both types of cross banding can be identified in hematoxylin and eosin or in azan stains; a much better visualization is obtained using the PTAH or the Luxol Fast Blue (LBF) method. Moreover, LFB, giving a selective blue staining of the damaged cells, allows the identification of the recently described diffuse type MFD. Well developed contraction bands may indicate the vitality of a heart trauma, yet a supravital occurrence seems to be possible. MFD, diffuse or cross band type, clearly correlates with high blood catecholamine levels at the time of death.
Topics: Cardiomyopathies; Heart Injuries; Humans; Myocardial Contraction; Myocardium; Myofibrils
PubMed: 2241797
DOI: No ID Found -
ELife Nov 2019Myofibrils are huge cytoskeletal assemblies embedded in the cytosol of muscle cells. They consist of arrays of sarcomeres, the smallest contractile unit of muscles....
Myofibrils are huge cytoskeletal assemblies embedded in the cytosol of muscle cells. They consist of arrays of sarcomeres, the smallest contractile unit of muscles. Within a muscle type, myofibril diameter is highly invariant and contributes to its physiological properties, yet little is known about the underlying mechanisms setting myofibril diameter. Here we show that the PDZ and LIM domain protein Zasp, a structural component of Z-discs, mediates Z-disc and thereby myofibril growth through protein oligomerization. Oligomerization is induced by an interaction of its ZM domain with LIM domains. Oligomerization is terminated upon upregulation of shorter Zasp isoforms which lack LIM domains at later developmental stages. The balance between these two isoforms, which we call growing and blocking isoforms sets the stereotyped diameter of myofibrils. If blocking isoforms dominate, myofibrils become smaller. If growing isoforms dominate, myofibrils and Z-discs enlarge, eventually resulting in large pathological aggregates that disrupt muscle function.
Topics: Animals; Carrier Proteins; Drosophila; Drosophila Proteins; Myofibrils; Protein Binding; Protein Domains; Protein Multimerization
PubMed: 31746737
DOI: 10.7554/eLife.50496 -
Advances in Experimental Medicine and... 2018Muscle tissue is a highly specialized type of tissue, made up of cells that have as their fundamental properties excitability and contractility. The cellular elements... (Review)
Review
Muscle tissue is a highly specialized type of tissue, made up of cells that have as their fundamental properties excitability and contractility. The cellular elements that make up this type of tissue are called muscle fibers, or myofibers, because of the elongated shape they have. Contractility is due to the presence of myofibrils in the muscle fiber cytoplasm, as large cellular assemblies. Also, myofibers are responsible for the force that the muscle generates which represents a countless aspect of human life. Movements due to muscles are based on the ability of muscle fibers to use the chemical energy procured in metabolic processes, to shorten and then to return to the original dimensions. We describe in detail the levels of organization for the myofiber, and we correlate the structural aspects with the functional ones, beginning with neuromuscular transmission down to the biochemical reactions achieved in the sarcoplasmic reticulum by the release of Ca and the cycling of crossbridges. Furthermore, we are reviewing the types of muscle contractions and the fiber-type classification.
Topics: Animals; Humans; Muscle Contraction; Muscles; Myofibrils; Sarcoplasmic Reticulum
PubMed: 30390246
DOI: 10.1007/978-981-13-1435-3_2 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2018The formation of myofibrils was analyzed in neonatal mouse cardiomyocytes grown in culture and stained with fluorescent antibodies directed against myofibrillar...
The formation of myofibrils was analyzed in neonatal mouse cardiomyocytes grown in culture and stained with fluorescent antibodies directed against myofibrillar proteins. The cardiomyocyte cultures also were exposed to siRNA probes to test the role of nonmuscle myosin IIB expression in the formation of myofibrils. In culture, new myofibrils formed in the spreading cell margins surrounding contractile myofibrils previously assembled in utero. Observations indicated that assembly of mature myofibrils occurred in three-stages, as previously reported in cultured mouse skeletal muscle. Premyofibrils, characterized by minisarcomeres with nonmuscle myosin IIB and muscle-specific alpha-actinin bound to actin filaments, formed in the first stage; followed by nascent myofibrils, the second stage when muscle myosin II and titin were first detected. In the mature myofibril stage muscle myosin II filaments aligned in periodic A-Bands; late assembling proteins, including myomesin and telethonin, were integrated in the sarcomeres, and nonmuscle IIB was absent from the sarcomeres. Treatment of the cultured neonatal cardiomyocytes with gene-specific siRNAs for nonmuscle myosin IIB, led to a marked decrease in the formation of premyofibrils, and subsequently of mature myofibrils. Anat Rec, 301:2067-2079, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Actins; Animals; Animals, Newborn; Cell Differentiation; Cells, Cultured; Mice; Myocytes, Cardiac; Myofibrils
PubMed: 30537042
DOI: 10.1002/ar.23961 -
BioEssays : News and Reviews in... Nov 2001This essay reviews the long tradition of experimental genetics of the Drosophila indirect flight muscles (IFM). It discusses how genetics can operate in tandem with... (Review)
Review
This essay reviews the long tradition of experimental genetics of the Drosophila indirect flight muscles (IFM). It discusses how genetics can operate in tandem with multidisciplinary approaches to provide a description, in molecular terms, of the functional properties of the muscle myofibril. In particular, studies at the interface of genetics and proteomics address protein function at the cellular scale and offer an outstanding platform with which to elucidate how the myofibril works. Two generalizations can be enunciated from the studies reviewed. First, the study of mutant IFM proteomes provides insight into how proteins are functionally organized in the myofibril. Second, IFM mutants can give rise to structural and contractile defects that are unrelated, a reflection of the dual function that myofibrillar proteins play as fundamental components of the sarcomeric framework and biochemical "parts" of the contractile "engine".
Topics: Animals; Drosophila; Flight, Animal; Insect Proteins; Muscle Proteins; Muscle, Skeletal; Myofibrils
PubMed: 11746221
DOI: 10.1002/bies.1150