Authors: Peter W Gunning, Edna C Hardeman

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

Authors: Zhen-Xing Wang, Xiao Lin, Jia Cao...

BACKGROUND

Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging.

RESULTS

Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo.

CONCLUSIONS

Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis.

Topics: Animals; Male; Mice; Adipogenesis; Cell Differentiation; Cells, Cultured; Extracellular Vesicles; Mesenchymal Stem Cells; Mice, Inbred C57BL; Mice, Transgenic; Osteoclasts; Osteocytes; Osteogenesis; Osteoporosis; Tropomyosin

PubMed: 38664789
DOI: 10.1186/s12951-024-02367-x

Review

Authors: Dietmar J Manstein, J C M Meiring, E C Hardeman...

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

Review

Authors: Kevin T Gray, Alla S Kostyukova, Thomas Fath...

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

Review

Authors: Nada Humayun-Zakaria, Roland Arnold, Anshita Goel...

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

Review

Authors: Miro Janco, Worawit Suphamungmee, Xiaochuan Li...

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

Authors: Eleni Peristeri, Efthimios Dardiotis

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

Authors: Mirjana Radomirović, Nikola Gligorijević, Dragana Stanić-Vučinić...

Tropomyosin is the major and predominant allergen among shellfish. This study developed an ultrasensitive immuno-PCR method for the quantification of crustacean tropomyosin in foods. The method couples sandwich ELISA with the real-time PCR (rtPCR) amplification of marker DNAs. Monoclonal anti-TPM antibody was the capture antibody, polyclonal rabbit anti-shrimp tropomyosin antibody was the detection antibody, while natural shrimp tropomyosin served as the standard. A double-stranded amino-DNA was covalently conjugated to a secondary anti-rabbit antibody and subsequently amplified and quantified via rtPCR. The quantification sensitivity of immuno-PCR was 20-fold higher than analogous ELISA, with LOQ 19.8 pg/mL. The developed immuno-PCR method is highly specific for the detection of crustacean tropomyosin and is highly precise in a broad concentration range. Tropomyosin recovery in the spiked vegetable soup was 87.7-115.6%. Crustacean tropomyosin was also quantified in commercial food products. The reported immuno-PCR assay is the most sensitive method for the quantification of crustacean tropomyosin and is the first immuno-PCR-based assay for the quantification of food allergen and food protein in general. The described method could be easily adapted for the specific and ultrasensitive immuno-PCR-based detection of traces of any food allergen that is currently being quantified with ELISA, which is of critical importance for people with food allergies.

Topics: Humans; Animals; Rabbits; Tropomyosin; Crustacea; Shellfish; Seafood; Allergens; Food Hypersensitivity

PubMed: 37895089
DOI: 10.3390/ijms242015410

Review

Authors: Olivia E McKenna, Claudia Asam, Galber R Araujo...

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

Authors: Steven Marston

In an article in this edition of the Journal of Muscle Research and Cell Motility, Geeves, Hitchcock-DiGregori and Gunning present a nomenclature founded on the gene and exon structure of tropomyosin that is both clear and unambiguous. Moreover, the authors have ensured that the new names are linked with their sequences in the NCBI database, thus eliminating the uncertainty of linking a protein isoform with its sequence. This nomenclature system has been planned with the support of all the major labs that work with tropomyosin. We recommend that all researchers take note of this scheme and use it.

Topics: Animals; Humans; Tropomyosin

PubMed: 25361644
DOI: 10.1007/s10974-014-9393-x