Review

Authors: Duygu Selcen

PURPOSE OF REVIEW

The aim of this communication is to provide an up-to-date overview of myofibrillar myopathies.

RECENT FINDINGS

The most important recent advance in the myofibrillar myopathies has been the discovery that mutations in Z band alternatively spliced PDZ-containing protein and filamin C, as well as in desmin, alphaB-crystallin and myotilin, result in similar pathologic alterations in skeletal muscle that are typical of myofibrillar myopathy. Despite the increasing genetic heterogeneity, the clinical and morphologic phenotypes are remarkably homogeneous. The typical clinical manifestation is slowly progressive proximal, distal or both proximal and distal limb muscle weakness. Cardiomyopathy can be associated and is sometimes the presenting finding. Peripheral neuropathy also occurs in some patients. In every myofibrillar myopathy, there is abnormal accumulation of an array of proteins at ectopic sites as well as accumulation of degraded myofibrillar proteins forming large aggregates. The key issue now is to analyze the molecular mechanisms underlying the cascade of events that destroy the myofibrillar architecture and trigger the aberrant expression of multiple proteins.

SUMMARY

Several disease genes have recently been recognized in myofibrillar myopathies. So far, the disease proteins identified are components of or chaperone for the Z-disk. In each case, the molecular defect leads to a stereotyped cascade of structural events in the muscle fiber.

Topics: Age of Onset; Connectin; Contractile Proteins; Cytoskeletal Proteins; Desmin; Filamins; Humans; Microfilament Proteins; Muscle Proteins; Muscle, Skeletal; Muscular Diseases; Myofibrils; alpha-Crystallins; beta-Crystallins

PubMed: 18769253
DOI: 10.1097/WCO.0b013e32830a752b

Review

Authors: Li Zhang, Amy Shaub Maddox

Topics: Contractile Proteins; Cytokinesis; History, 20th Century; Microfilament Proteins; Models, Molecular

PubMed: 20178751
DOI: 10.1016/j.cub.2009.12.017

Review

Authors: Corina Dekraker, Eric Boucher, Craig A Mandato...

Cytokinesis and single-cell wound repair both involve contractile assemblies of filamentous actin (F-actin) and myosin II organized into characteristic ring-like arrays. The assembly of these actomyosin contractile rings (CRs) is specified spatially and temporally by small Rho GTPases, which trigger local actin polymerization and myosin II contractility via a variety of downstream effectors. We now have a much clearer view of the Rho GTPase signaling cascade that leads to the formation of CRs, but some factors involved in CR positioning, assembly, and function remain poorly understood. Recent studies show that this regulation is multifactorial and goes beyond the long-established Ca -dependent processes. There is substantial evidence that the Ca -independent changes in cell shape, tension, and plasma membrane composition that characterize cytokinesis and single-cell wound repair also regulate CR formation. Elucidating the regulation and mechanistic properties of CRs is important to our understanding of basic cell biology and holds potential for therapeutic applications in human disease. In this review, we present a primer on the factors influencing and regulating CR positioning, assembly, and contraction as they occur in a variety of cytokinetic and single-cell wound repair models. Anat Rec, 301:2051-2066, 2018. © 2018 Wiley Periodicals, Inc.

Topics: Actin Cytoskeleton; Actomyosin; Animals; Cell Membrane; Contractile Proteins; Cytokinesis; Humans; Tissue Scaffolds; Wound Healing

PubMed: 30312008
DOI: 10.1002/ar.23962

Review

Authors: H Neimark

The basis of gliding motility in prokaryotes including certain mycoplasmas and the ability of mycoplasmas to retain their characteristic cell shapes in the absence of a supporting cell wall is unexplained. This review examines the available studies describing proteins resembling contractile proteins and cytoskeletal proteins in prokaryotes. Proteins with a significant degree of amino acid sequence homology to the myofibrillar proteins actin and myosin Al light chain and to tropomyosin have been described in prokaryotes. In addition, protein preparations from Mycoplasma pneumoniae have been shown to bind heavy meromyosin fragments, anti-actin antibody, and phalloidin; however, it remains to be proved that proteins in these preparations sharing properties with actin are synthesized by the mycoplasma.

Topics: Actins; Bacterial Proteins; Contractile Proteins; Cytochalasins; Fluorescent Antibody Technique; Mycoplasma; Mycoplasma pneumoniae; Mycoplasmatales; Peptide Elongation Factor Tu; Peptide Elongation Factors

PubMed: 6433566
DOI: No ID Found

Review

Authors: Oksana P Gerzen, Veronika O Votinova, Iulia K Potoskueva...

The binding of calcium and magnesium ions to proteins is crucial for regulating heart contraction. However, other divalent cations, including xenobiotics, can accumulate in the myocardium and enter cardiomyocytes, where they can bind to proteins. In this article, we summarized the impact of these cations on myosin ATPase activity and EF-hand proteins, with special attention given to toxic cations. Optimal binding to EF-hand proteins occurs at an ionic radius close to that of Mg and Ca. In skeletal Troponin C, Cd, Sr, Pb, Mn, Co, Ni, Ba, Mg, Zn, and trivalent lanthanides can substitute for Ca. As myosin ATPase is not a specific MgATPase, Ca, Fe, Mn, Ni, and Sr could support myosin ATPase activity. On the other hand, Zn and Cu significantly inhibit ATPase activity. The affinity to various divalent cations depends on certain proteins or their isoforms and can alter with amino acid substitution and post-translational modification. Cardiac EF-hand proteins and the myosin ATP-binding pocket are potential molecular targets for toxic cations, which could significantly alter the mechanical characteristics of the heart muscle at the molecular level.

Topics: Cations, Divalent; Contractile Proteins; Heart; Myosins; Cations; Calcium

PubMed: 37445756
DOI: 10.3390/ijms241310579

Authors: Reshma Davidson, Yajun Liu, Kenneth S Gerien...

Single-cell microscopy provides a powerful tool to visualize cellular and subcellular processes in wild-type and mutant cells by observing fluorescently tagged proteins. Here, we describe three simple methods to visualize fission yeast cells: gelatin slides, coverslip-bottom dishes, and tetrad fluorescence microscopy. These imaging methods and data analysis using free software make it possible to quantify protein localization, dynamics, and concentration with high spatial and temporal resolution. In fission yeast, the actomyosin contractile ring is essential for cytokinesis. We use the visualization and quantification of contractile ring proteins as an example to demonstrate how to use these methods.

Topics: Contractile Proteins; Microscopy, Fluorescence; Molecular Imaging; Schizosaccharomyces; Schizosaccharomyces pombe Proteins

PubMed: 26519302
DOI: 10.1007/978-1-4939-3145-3_2

Review

Authors: Ziba Razinia, Toni Mäkelä, Jari Ylänne...

Filamins are essential, evolutionarily conserved, modular, multidomain, actin-binding proteins that organize the actin cytoskeleton and maintain extracellular matrix connections by anchoring actin filaments to transmembrane receptors. By cross-linking and anchoring actin filaments, filamins stabilize the plasma membrane, provide cellular cortical rigidity, and contribute to the mechanical stability of the plasma membrane and the cell cortex. In addition to binding actin, filamins interact with more than 90 other binding partners including intracellular signaling molecules, receptors, ion channels, transcription factors, and cytoskeletal and adhesion proteins. Thus, filamins scaffold a wide range of signaling pathways and are implicated in the regulation of a diverse array of cellular functions including motility, maintenance of cell shape, and differentiation. Here, we review emerging structural and functional evidence that filamins are mechanosensors and/or mechanotransducers playing essential roles in helping cells detect and respond to physical forces in their local environment.

Topics: Animals; Cell Membrane; Cell Movement; Cell Shape; Contractile Proteins; Cytoskeleton; Filamins; Humans; Mechanotransduction, Cellular; Microfilament Proteins; Protein Binding; Protein Structure, Tertiary; Signal Transduction

PubMed: 22404683
DOI: 10.1146/annurev-biophys-050511-102252

Review

Authors: Clarissa S Craft, Thomas J Broekelmann, Robert P Mecham...

Microfibril-associated glycoproteins 1 and 2 (MAGP-1, MAGP-2) are protein components of extracellular matrix microfibrils. These proteins interact with fibrillin, the core component of microfibrils, and impart unique biological properties that influence microfibril function in vertebrates. MAGPs bind active forms of TGFβ and BMPs and are capable of modulating Notch signaling. Mutations in MAGP-1 or MAGP-2 have been linked to thoracic aneurysms and metabolic disease in humans. MAGP-2 has also been shown to be an important biomarker in several human cancers. Mice lacking MAGP-1 or MAGP-2 have defects in multiple organ systems, which reflects the widespread distribution of microfibrils in vertebrate tissues. This review summarizes our current understanding of the function of the MAGPs and their relationship to human disease.

Topics: Animals; Aortic Aneurysm, Thoracic; Biomarkers; Bone Morphogenetic Proteins; Contractile Proteins; Extracellular Matrix; Extracellular Matrix Proteins; Humans; Metabolic Diseases; Mice; Mutation; Neoplasms; RNA Splicing Factors; Receptors, Notch; Signal Transduction; Transforming Growth Factor beta

PubMed: 29524629
DOI: 10.1016/j.matbio.2018.03.006

Review

Authors: T D Pollard

Topics: Actins; Actomyosin; Adenosine Triphosphatases; Animals; Calcium; Cell Division; Cell Movement; Contractile Proteins; Cytochalasins; Cytoplasm; Cytoplasmic Streaming; Cytoskeleton; Gels; Macromolecular Substances; Microtubules; Myosins; Phalloidine; Protein Conformation

PubMed: 6459328
DOI: 10.1083/jcb.91.3.156s

Review

Authors: Zi-Sen Zhang, He-Nan Zhou, Shuang-Shuang He...

Pericyte, a kind of pluripotent cell, may regulate the irrigation flow and permeability of microcirculation. Pericytes are similar to the smooth muscle cells, which express several kinds of contractile proteins and have contractility. The dysfunction of pericytes is related to many microvascular diseases, including hypoxia, hypertension, diabetic retinopathy, fibrosis, inflammation, Alzheimer's disease, multiple sclerosis, and tumor formation. For a long time, their existence and function have been neglected. The distribution, structure, biomarker, related signaling pathways as well as the roles of pericytes on vascular diseases will be introduced in this review.

Topics: Contractile Proteins; Humans; Microcirculation; Pericytes; Research; Vascular Diseases

PubMed: 32192909
DOI: 10.1016/j.cjtee.2020.02.006