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Current Biology : CB Jan 2017The actin cytoskeleton provides not only the underpinning for cell architecture but also mechanical force and the ability to drive movement of cells and their...
The actin cytoskeleton provides not only the underpinning for cell architecture but also mechanical force and the ability to drive movement of cells and their organelles. It is tempting to think of it simply as a set of stable structural elements, but nothing could be further from the truth. The cells of our bodies are continually remodelling their architecture by responding to a range of imposed biomechanical forces and intracellular functional demands. Studies of the dynamic and functional properties of the actin cytoskeleton have been dominated by a focus on actin and the view that actin filaments are essentially 'generic'. However, the 'other' component of most actin filaments in animals - tropomyosin - is coming into prominence. With this discovery is the realisation that far from being generic, actin filaments have their own functional individuality provided to them by their associated tropomyosin. This is changing the way we understand and study the actin cytoskeleton and has delivered a new therapeutic opportunity in what had come to be considered a 'no-go zone'.
Topics: Actin Cytoskeleton; Animals; Biological Evolution; Tropomyosin
PubMed: 28073025
DOI: 10.1016/j.cub.2016.11.033 -
Journal of Muscle Research and Cell... Mar 2020The interactions of cytoskeletal actin filaments with myosin family motors are essential for the integrity and function of eukaryotic cells. They support a wide range of... (Review)
Review
The interactions of cytoskeletal actin filaments with myosin family motors are essential for the integrity and function of eukaryotic cells. They support a wide range of force-dependent functions. These include mechano-transduction, directed transcellular transport processes, barrier functions, cytokinesis, and cell migration. Despite the indispensable role of tropomyosins in the generation and maintenance of discrete actomyosin-based structures, the contribution of individual cytoskeletal tropomyosin isoforms to the structural and functional diversification of the actin cytoskeleton remains a work in progress. Here, we review processes that contribute to the dynamic sorting and targeted distribution of tropomyosin isoforms in the formation of discrete actomyosin-based structures in animal cells and their effects on actin-based motility and contractility.
Topics: Actins; Humans; Tropomyosin
PubMed: 31054005
DOI: 10.1007/s10974-019-09514-0 -
International Journal of Molecular... Feb 2021We are pleased to announce a Special Issue on the Genetic Basis and Epidemiology of Myopathies. This Special Issue is collecting papers pertaining to various lines of...
We are pleased to announce a Special Issue on the Genetic Basis and Epidemiology of Myopathies. This Special Issue is collecting papers pertaining to various lines of research focusing on the genetic basis and the epidemiology of myopathies. The Guest Editors' note combines the contributing authors' reviews and findings of relevant research, and we hope that future studies on myopathies will attempt to confirm these findings and, additionally, evaluate supplementary phenotypic and histological expressions of myopathies, as well as genetic factors in their pathogenesis.
Topics: Animals; Disease Models, Animal; Genetic Association Studies; Humans; Muscular Diseases; Mutation; Transcription Factors; Tropomyosin
PubMed: 33671495
DOI: 10.3390/ijms22042152 -
International Journal of Molecular... Mar 2019Despite the incidence and prevalence of urothelial bladder cancer (UBC), few advances in treatment and diagnosis have been made in recent years. In this review, we... (Review)
Review
Despite the incidence and prevalence of urothelial bladder cancer (UBC), few advances in treatment and diagnosis have been made in recent years. In this review, we discuss potential biomarker candidates: the tropomyosin family of genes, encoded by four loci in the human genome. The expression of these genes is tissue-specific. Tropomyosins are responsible for diverse cellular roles, most notably based upon their interplay with actin to maintain cellular processes, integrity and structure. Tropomyosins exhibit a large variety of splice forms, and altered isoform expression levels have been associated with cancer, including UBC. Notably, tropomyosin isoforms are detectable in urine, offering the potential for non-invasive diagnosis and risk-stratification. This review collates the basic knowledge on tropomyosin and its isoforms, and discusses their relationships with cancer-related phenomena, most specifically in UBC.
Topics: Biomarkers, Tumor; Cell Movement; Gene Expression Regulation, Neoplastic; Genome, Human; Humans; Multigene Family; Protein Isoforms; Tropomyosin; Urinary Bladder Neoplasms
PubMed: 30836651
DOI: 10.3390/ijms20051102 -
Molecular and Cellular Neurosciences Oct 2017Actin is a profoundly influential protein; it impacts, among other processes, membrane morphology, cellular motility, and vesicle transport. Actin can polymerize into... (Review)
Review
Actin is a profoundly influential protein; it impacts, among other processes, membrane morphology, cellular motility, and vesicle transport. Actin can polymerize into long filaments that push on membranes and provide support for intracellular transport. Actin filaments have polar ends: the fast-growing (barbed) end and the slow-growing (pointed) end. Depolymerization from the pointed end supplies monomers for further polymerization at the barbed end. Tropomodulins (Tmods) cap pointed ends by binding onto actin and tropomyosins (Tpms). Tmods and Tpms have been shown to regulate many cellular processes; however, very few studies have investigated their joint role in the nervous system. Recent data directly indicate that they can modulate neuronal morphology. Additional studies suggest that Tmod and Tpm impact molecular processes influential in synaptic signaling. To facilitate future research regarding their joint role in actin regulation in the nervous system, we will comprehensively discuss Tpm and Tmod and their known functions within molecular systems that influence neuronal development.
Topics: Actins; Animals; Cytoskeleton; Humans; Morphogenesis; Neurons; Tropomodulin; Tropomyosin
PubMed: 28433463
DOI: 10.1016/j.mcn.2017.04.002 -
Journal of Muscle Research and Cell... Aug 2013Tropomyosins (Tm) in humans are expressed from four distinct genes and by alternate splicing >40 different Tm polypeptide chains can be made. The functional Tm unit is a... (Review)
Review
Tropomyosins (Tm) in humans are expressed from four distinct genes and by alternate splicing >40 different Tm polypeptide chains can be made. The functional Tm unit is a dimer of two parallel polypeptide chains and these can be assembled from identical (homodimer) or different (heterodimer) polypeptide chains provided both chains are of the same length. Since most cells express multiple isoforms of Tm, the number of different homo and heterodimers that can be assembled becomes very large. We review the mechanism of dimer assembly and how preferential assembly of some heterodimers is driven by thermodynamic stability. We examine how in vitro studies can reveal functional differences between Tm homo and heterodimers (stability, actin affinity, flexibility) and the implication for how there could be selection of Tm isomers in the assembly on to an actin filament. The role of Tm heterodimers becomes more complex when mutations in Tm are considered, such as those associated with cardiomyopathies, since mutations can appear in only one of the chains.
Topics: Actins; Animals; Humans; Polymorphism, Genetic; Protein Isoforms; Structure-Activity Relationship; Tropomyosin
PubMed: 23832280
DOI: 10.1007/s10974-013-9353-x -
Disease Markers 2022To investigate the correlation between tropomyosin (TM) and clinical characteristics of bladder cancer. In addition, the relationship between TM and immune cell...
OBJECTIVE
To investigate the correlation between tropomyosin (TM) and clinical characteristics of bladder cancer. In addition, the relationship between TM and immune cell infiltration in bladder cancer was further analyzed.
METHODS
Based on The Cancer Genome Atlas (TCGA) database, the relationship between TM expression and clinicopathological features in bladder cancer was analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the value of TM as a diagnostic marker for bladder cancer. Univariate and multivariate Cox regression was used to analyze the independent factors affecting the prognosis of patients with bladder cancer. The relationship between TM and immune cell infiltration was analyzed.
RESULTS
ROC curve showed that TPM1, TPM2, and TPM3 had significant diagnostic ability (AUC was 0.845, 0.848, and 0.873, respectively). The high expression of TPM1 and TPM2 is associated with poor overall and disease-specific survival in patients with bladder cancer ( < 0.05). Multivariate Cox analysis showed that age and TPM1 were independent prognostic factors. The expression levels of TPM1, TPM2, TPM3, and TPM4 in low grade bladder cancer were lower than those in high grade bladder cancer ( < 0.05). TPM1 and TPM2 are positively correlated with the infiltration of macrophages and NK cells in bladder cancer. TPM3 is positively associated with Th2. TPM4 is positively correlated with Th1 cells, macrophages, and neutrophils ( < 0.05).
CONCLUSIONS
TPM1 and TPM2 are effective markers for the diagnosis of bladder cancer. TPM1 is an independent prognostic factor for bladder cancer. TM is also associated with the infiltration of various immune cells in bladder cancer. TM may have influenced the development of bladder cancer through immune inhibition.
Topics: Biomarkers; Humans; Prognosis; Protein Isoforms; Tropomyosin; Urinary Bladder Neoplasms
PubMed: 35734544
DOI: 10.1155/2022/6936262 -
Pediatric Allergy and Immunology :... Sep 2016Panallergens comprise various protein families of plant as well as animal origin and are responsible for wide IgE cross-reactivity between related and unrelated... (Review)
Review
Panallergens comprise various protein families of plant as well as animal origin and are responsible for wide IgE cross-reactivity between related and unrelated allergenic sources. Such cross-reactivities include reactions between various pollen sources, pollen and plant-derived foods as well as invertebrate-derived inhalants and foodstuff. Here, we provide an overview on the most clinically relevant panallergens from plants (profilins, polcalcins, non-specific lipid transfer proteins, pathogenesis-related protein family 10 members) and on the prominent animal-derived panallergen family, tropomyosins. In addition, we explore the role of panallergens in the sensitization process and progress of the allergic disease. Emphasis is given on epidemiological aspects of panallergen sensitization and clinical manifestations. Finally, the issues related to diagnosis and therapy of patients sensitized to panallergens are outlined, and the use of panallergens as predictors for cross-reactive allergy and as biomarkers for disease severity is discussed.
Topics: Allergens; Animals; Antigens, Plant; Biomarkers; Cross Reactions; Food; Humans; Hypersensitivity; Immunoglobulin E; Pollen; Predictive Value of Tests; Tropomyosin
PubMed: 27129102
DOI: 10.1111/pai.12589 -
Bioarchitecture 2013Tropomyosin is an actin binding protein that regulates actin filament dynamics and its interactions with actin binding proteins such as myosin, tropomodulin, formin,... (Review)
Review
Tropomyosin is an actin binding protein that regulates actin filament dynamics and its interactions with actin binding proteins such as myosin, tropomodulin, formin, Arp2/3 and ADF-cofilin in most eukaryotic cells. Tropomyosin is the prototypical two-chained, α-helical coiled coil protein that associates end-to-end and binds to both sides of the actin filament. Each tropomyosin molecule spans four to seven actin monomers in the filament, depending on the size of the tropomyosin. Tropomyosins have a periodic heptad repeat sequence that is characteristic of coiled coil proteins as well as additional periodicities required for its interaction with the actin filament, where each periodic repeat interacts with one actin molecule. This review addresses the role of periodic features of the Tm molecule in carrying out its universal functions of binding to the actin filament and its regulation and the specific features that may determine the isoform specificity of tropomyosins.
Topics: Actins; Amino Acid Sequence; Animals; Humans; Protein Binding; Protein Structure, Secondary; Tropomyosin
PubMed: 23887197
DOI: 10.4161/bioa.25616 -
Biophysical Journal Jan 2021Recently, our understanding of the structural basis of troponin-tropomyosin's Ca-triggered regulation of striated muscle contraction has advanced greatly, particularly... (Review)
Review
Recently, our understanding of the structural basis of troponin-tropomyosin's Ca-triggered regulation of striated muscle contraction has advanced greatly, particularly via cryo-electron microscopy data. Compelling atomic models of troponin-tropomyosin-actin were published for both apo- and Ca-saturated states of the cardiac thin filament. Subsequent electron microscopy and computational analyses have supported and further elaborated the findings. Per cryo-electron microscopy, each troponin is highly extended and contacts both tropomyosin strands, which lie on opposite sides of the actin filament. In the apo-state characteristic of relaxed muscle, troponin and tropomyosin hinder strong myosin-actin binding in several different ways, apparently barricading the actin more substantially than does tropomyosin alone. The troponin core domain, the C-terminal third of TnI, and tropomyosin under the influence of a 64-residue helix of TnT located at the overlap of adjacent tropomyosins are all in positions that would hinder strong myosin binding to actin. In the Ca-saturated state, the TnI C-terminus dissociates from actin and binds in part to TnC; the core domain pivots significantly; the N-lobe of TnC binds specifically to actin and tropomyosin; and tropomyosin rotates partially away from myosin's binding site on actin. At the overlap domain, Ca causes much less tropomyosin movement, so a more inhibitory orientation persists. In the myosin-saturated state of the thin filament, there is a large additional shift in tropomyosin, with molecular interactions now identified between tropomyosin and both actin and myosin. A new era has arrived for investigation of the thin filament and for functional understandings that increasingly accommodate the recent structural results.
Topics: Actin Cytoskeleton; Actins; Calcium; Cryoelectron Microscopy; Models, Molecular; Muscle Contraction; Muscle, Striated; Tropomyosin; Troponin
PubMed: 33221250
DOI: 10.1016/j.bpj.2020.11.014