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Myosin II

Ryan J Colquhoun, Mitchel A Magrini, Cody T Haun, Tyler W D Muddle, Patrick M Tomko, Micheal J Luera, Cameron S Mackey, Christopher G Vann, Jeffrey S Martin, Kaelin C Young, Jason M DeFreitas, Michael D Roberts, Nathaniel D M Jenkins
Previous investigations have reported a relationship between skeletal muscle phenotype and motor unit (MU) firing parameters during submaximal contractions. The purpose of the current investigation, however, was to examine the relationships between motor unit firing behavior during a maximal voluntary contraction, Myosin Heavy Chain (MHC) isoform content, and various molecular neuromuscular targets of the vastus lateralis (VL) muscle in resistance-trained men. Ten resistance-trained males completed a trapezoidal ramp contraction up to 100% of their maximal voluntary isometric strength (MVIC)...
March 2018: Physiological Reports
Louise P Cramer, Robert R Kay, Evgeny Zatulovskiy
Attractive and repulsive cell guidance is essential for animal life and important in disease. Cell migration toward attractants dominates studies [1-8], but migration away from repellents is important in biology yet relatively little studied [5, 9, 10]. It is widely held that cells initiate migration by protrusion of their front [11-15], yet this has not been explicitly tested for cell guidance because cell margin displacement at opposite ends of the cell has not been distinguished for any cue. We argue that protrusion of the front, retraction of the rear, or both together could in principle break cell symmetry and start migration in response to guidance cues [16]...
March 7, 2018: Current Biology: CB
Hong-Qiang Chen, Ji Zhao, Yan Li, Li-Xiong He, Yu-Jing Huang, Wei-Qun Shu, Jia Cao, Wen-Bin Liu, Jin-Yi Liu
Microcystin (MC) is a cyclic heptapeptide compound which could lead to the development of hepatocellular carcinoma. However, the underlying epigenetic regulation mechanism is largely unknown. In this study, microcystin-LR (L: lysine, R: arginine, MC-LR) was used to induce the malignant transformation of human hepatocyte L02 cell line. The profile of gene expression, microRNA (miRNA) and DNA methylation were detected through high-throughput sequencing. Compared with control group, the expression of 826 genes and 187 miRNAs changed significantly in MC-LR treated group...
March 5, 2018: Toxicology Letters
Nadia Efimova, Tatyana M Svitkina
Adherens junctions (AJs) are mechanosensitive cadherin-based intercellular adhesions that interact with the actin cytoskeleton and carry most of the mechanical load at cell-cell junctions. Both Arp2/3 complex-dependent actin polymerization generating pushing force and nonmuscle myosin II (NMII)-dependent contraction producing pulling force are necessary for AJ morphogenesis. Which actin system directly interacts with AJs is unknown. Using platinum replica electron microscopy of endothelial cells, we show that vascular endothelial (VE)-cadherin colocalizes with Arp2/3 complex-positive actin networks at different AJ types and is positioned at the interface between two oppositely oriented branched networks from adjacent cells...
March 5, 2018: Journal of Cell Biology
Bipasha Barua, Maria Sckolnick, Howard D White, Kathleen M Trybus, Sarah E Hitchcock-DeGregori
Muscle contraction, cytokinesis, cellular movement, and intracellular transport depend on regulated actin-myosin interaction. Most actin filaments bind one or more isoform of tropomyosin, a coiled-coil protein that stabilizes the filaments and regulates interactions with other actin-binding proteins, including myosin. Isoform-specific allosteric regulation of muscle myosin II by actin-tropomyosin is well-established while that of processive myosins, such as myosin V, which transport organelles and macromolecules in the cell periphery, is less certain...
March 3, 2018: Cytoskeleton
Anand Prakash Singh, Swati Sharma, Kirti Pagarware, Rafay Anwar Siraji, Imran Ansari, Anupam Mandal, Pangertoshi Walling, Saima Aijaz
Enteropathogenic E. coli infection is characterized by rapid onset of diarrhea but the underlying mechanisms are not well defined. EPEC targets the tight junctions which selectively regulate the permeability of charged and uncharged molecules. Cooperative actions of the EPEC effectors EspF and Map have been reported to mediate tight junction disruption. To analyze the individual contributions of EspF and Map, we generated in vitro models where EspF and Map, derived from the EPEC strain E2348/69, were constitutively expressed in epithelial cells...
February 27, 2018: Scientific Reports
Patrick W Oakes, Tamara C Bidone, Yvonne Beckham, Austin V Skeeters, Guillermina R Ramirez-San Juan, Stephen P Winter, Gregory A Voth, Margaret L Gardel
The ability of adherent cells to sense changes in the mechanical properties of their extracellular environments is critical to numerous aspects of their physiology. It has been well documented that cell attachment and spreading are sensitive to substrate stiffness. Here, we demonstrate that this behavior is actually biphasic, with a transition that occurs around a Young's modulus of ∼7 kPa. Furthermore, we demonstrate that, contrary to established assumptions, this property is independent of myosin II activity...
February 27, 2018: Proceedings of the National Academy of Sciences of the United States of America
Andrius Masedunskas, Mark A Appaduray, Christine A Lucas, María Lastra Cagigas, Marco Heydecker, Mira Holliday, Joyce Meiring, Jeff Hook, Anthony Kee, Melissa White, Paul Thomas, Yingfan Zhang, Robert S Adelstein, Tobias Meckel, Till Böcking, Roberto Weigert, Nicole S Bryce, Peter W Gunning, Edna C Hardeman
Many actin filaments in animal cells are co-polymers of actin and tropomyosin. For many of these co-polymers, non-muscle myosin II associates to establish a contractile network. However, the temporal relationship of these 3 proteins in the de novo assembly of actin filaments is not known. Intravital subcellular microscopy of secretory granule exocytosis allows the visualisation and quantitation of the formation of an actin scaffold in real time with the added advantage that it occurs in a living mammal, under physiological conditions...
February 27, 2018: Journal of Cell Science
Masahiro Kuragano, Yota Murakami, Masayuki Takahashi
Nonmuscle myosin II (NMII) plays an essential role in directional cell migration. In this study, we investigated the roles of NMII isoforms (NMIIA and NMIIB) in the migration of human embryonic lung fibroblasts, which exhibit directionally persistent migration in an intrinsic manner. NMIIA-knockdown (KD) cells migrated unsteadily, but their direction of migration was approximately maintained. By contrast, NMIIB-KD cells occasionally reversed their direction of migration. Lamellipodium-like protrusions formed in the posterior region of NMIIB-KD cells prior to reversal of the migration direction...
February 24, 2018: Biochemical and Biophysical Research Communications
Chwee Tat Koe, Ye Sing Tan, Max Lönnfors, Seong Kwon Hur, Christine Siok Lan Low, Yingjie Zhang, Pakorn Kanchanawong, Vytas A Bankaitis, Hongyan Wang
A central feature of most stem cells is the ability to self-renew and undergo differentiation via asymmetric division. However, during asymmetric division the role of phosphatidylinositol (PI) lipids and their regulators is not well established. Here, we show that the sole type I PI transfer protein, Vibrator, controls asymmetric division of Drosophila neural stem cells (NSCs) by physically anchoring myosin II regulatory light chain, Sqh, to the NSC cortex. Depletion of vib or disruption of its lipid binding and transfer activities disrupts NSC polarity...
February 27, 2018: ELife
Wendy Rosales, Fernando Lizcano
The development of cardiovascular pathologies is partly attributed to epigenetic causes, including histone methylation, which appears to be an important marker in hearts that develop cardiac hypertrophy. Previous studies showed that the histone demethylase JMJD2A can regulate the hypertrophic process in murine cardiomyocytes. However, the influence of JMJD2A on cardiac hypertrophy in a human cardiomyocyte model is still poorly understood. In the present study, cardiomyocytes derived from human induced pluripotent stem cells (iPSCs) were used...
2018: Frontiers in Genetics
Tatyana M Svitkina
The actin cytoskeleton is the primary force-generating machinery in the cell, which can produce pushing (protrusive) forces using energy of actin polymerization and pulling (contractile) forces via sliding of bipolar filaments of myosin II along actin filaments, as well as perform other key functions. These functions are essential for whole cell migration, cell interaction with the environment, mechanical properties of the cell surface and other key aspects of cell physiology. The actin cytoskeleton is a highly complex and dynamic system of actin filaments organized into various superstructures by multiple accessory proteins...
February 21, 2018: Current Opinion in Cell Biology
Yi Yu, Yuyan Xiong, Jean-Pierre Montani, Zhihong Yang, Xiu-Fen Ming
Type-II L-arginine:ureahydrolase, arginase-II (Arg-II), is shown to activate mechanistic target of rapamycin complex 1 (mTORC1) pathway and contributes to cell senescence and apoptosis. In an attempt to elucidate the underlying mechanism, we identified myosin-1b (Myo1b) as a mediator. Overexpression of Arg-II induces re-distribution of lysosome and mTOR but not of tuberous sclerosis complex (TSC) from perinuclear area to cell periphery, dissociation of TSC from lysosome and activation of mTORC1-ribosomal protein S6 kinase 1 (S6K1) pathway...
February 22, 2018: Cell Death & Disease
Masahiro Kuragano, Taro Qp Uyeda, Keiju Kamijo, Yota Murakami, Masayuki Takahashi
Stress fibers (SFs) are contractile, force-generating bundled structures that can be classified into three subtypes, namely, ventral SFs (vSFs), transverse arcs (TAs), and dorsal SFs. Nonmuscle myosin II (NMII) is the main component of SFs. This study examined the roles of the NMII isoforms NMIIA and NMIIB in the organization of each SF subtype in immortalized fibroblasts. Knockdown (KD) of NMIIA (a major isoform) resulted in loss of TAs from the lamella and caused the lamella to lose its flattened shape. Exogenous expression of NMIIB rescued this defect in TA formation...
February 21, 2018: Molecular Biology of the Cell
Kyoung Hwan Lee, Guidenn Sulbarán, Shixin Yang, Ji Young Mun, Lorenzo Alamo, Antonio Pinto, Osamu Sato, Mitsuo Ikebe, Xiong Liu, Edward D Korn, Floyd Sarsoza, Sanford I Bernstein, Raúl Padrón, Roger Craig
Electron microscope studies have shown that the switched-off state of myosin II in muscle involves intramolecular interaction between the two heads of myosin and between one head and the tail. The interaction, seen in both myosin filaments and isolated molecules, inhibits activity by blocking actin-binding and ATPase sites on myosin. This interacting-heads motif is highly conserved, occurring in invertebrates and vertebrates, in striated, smooth, and nonmuscle myosin IIs, and in myosins regulated by both Ca 2+ binding and regulatory light-chain phosphorylation...
February 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
Xingwang Xie, Xueyan Wang, Weijia Liao, Ran Fei, Nan Wu, Xu Cong, Qian Chen, Lai Wei, Yu Wang, Hongsong Chen
BACKGROUND: Identification of novel MDM2 or p53 binding proteins may reveal undefined oncogenes, tumor suppressors, signaling pathways and possible treatment targets. METHODS: By means of immunoprecipitation and Mass Spectrometry analysis, we aimed to identify novel regulators of the MDM2-p53 pathway. We further clarified the impact of MYL6B on the p53 protein level and on the process of apoptosis. We also investigated the role of MYL6B in hepatocellular carcinoma by clone formation assay and by determining the correlation between its expression and prognosis of HCC patients...
February 13, 2018: Journal of Experimental & Clinical Cancer Research: CR
Tanbin Liu, Yi Hu, Shiyin Guo, Lei Tan, Yang Zhan, Lingchen Yang, Wei Liu, Naidong Wang, Yalan Li, Yingfan Zhang, Chengyu Liu, Yi Yang, Robert S Adelstein, Aibing Wang
Targeted integration of exogenous genes into so-called safe harbors/friend sites, offers the advantages of expressing normal levels of target genes and preventing potentially adverse effects on endogenous genes. However, the ideal genomic loci for this purpose remain limited. Additionally, due to the inherent and unresolved issues with the current genome editing tools, traditional embryonic stem (ES) cell-based targeted transgenesis technology is still preferred in practical applications. Here, we report that a high and repeatable homologous recombination (HR) frequency (>95%) is achieved when an approximate 6kb DNA sequence flanking the MYH9 gene exon 2 site is used to create the homology arms for the knockout/knock-in of diverse nonmuscle myosin II (NM II) isoforms in mouse ES cells...
2018: PloS One
Hervé Alégot, Pierre Pouchin, Olivier Bardot, Vincent Mirouse
Tissue elongation and its control by spatiotemporal signals is a major developmental question. Currently, it is thought that Drosophila ovarian follicular epithelium elongation requires the planar polarization of the basal domain cytoskeleton and of the extra-cellular matrix, associated with a dynamic process of rotation around the anteroposterior axis. Here we show, by careful kinetic analysis of fat2 mutants, that neither basal planar polarization nor rotation is required during a first phase of follicle elongation...
February 8, 2018: ELife
Pasquale Cervero, Christiane Wiesner, Anais Bouissou, Renaud Poincloux, Stefan Linder
Subcellular fine-tuning of the actomyosin cytoskeleton is a prerequisite for polarized cell migration. We identify LSP (lymphocyte-specific protein) 1 as a critical regulator of actomyosin contractility in primary macrophages. LSP1 regulates adhesion and migration, including the parameters cell area and speed, and also podosome turnover, oscillation and protrusive force. LSP1 recruits myosin IIA and its regulators, including myosin light chain kinase and calmodulin, and competes with supervillin, a myosin hyperactivator, for myosin regulators, and for actin isoforms, notably β-actin...
February 6, 2018: Nature Communications
Jiao Li, Zheng Wang, Qiqi Chu, Kewu Jiang, Juan Li, Nan Tang
The differentiation of alveolar epithelial type I (AT1) and type II (AT2) cells is essential for the lung gas exchange function. Disruption of this process results in neonatal death or in severe lung diseases that last into adulthood. We developed live imaging techniques to characterize the mechanisms that control alveolar epithelial cell differentiation. We discovered that mechanical forces generated from the inhalation of amniotic fluid by fetal breathing movements are essential for AT1 cell differentiation...
February 5, 2018: Developmental Cell
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