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https://www.readbyqxmd.com/read/28732005/filamin-actin-binding-and-titin-binding-fulfill-distinct-functions-in-z-disc-cohesion
#1
Nicanor González-Morales, Tristan K Holenka, Frieder Schöck
Many proteins contribute to the contractile properties of muscles, most notably myosin thick filaments, which are anchored at the M-line, and actin thin filaments, which are anchored at the Z-discs that border each sarcomere. In humans, mutations in the actin-binding protein Filamin-C result in myopathies, but the underlying molecular function is not well understood. Here we show using Drosophila indirect flight muscle that the filamin ortholog Cheerio in conjunction with the giant elastic protein titin plays a crucial role in keeping thin filaments stably anchored at the Z-disc...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28731162/a-homozygous-myo7a-mutation-associated-to-usher-syndrome-and-unilateral-auditory-neuropathy-spectrum-disorder
#2
Hong Xia, Pengzhi Hu, Lamei Yuan, Wei Xiong, Hongbo Xu, Junhui Yi, Zhijian Yang, Xiong Deng, Yi Guo, Hao Deng
Usher syndrome (USH) is an autosomal recessive disorder characterized by sensorineural hearing loss, progressive visual loss and night blindness due to retinitis pigmentosa (RP), with or without vestibular dysfunction. The purpose of this study was to detect the causative gene in a consanguineous Chinese family with USH. A c.3696_3706del (p.R1232Sfs*72) variant in the myosin VIIa gene (MYO7A) was identified in the homozygous state by exome sequencing. The co‑segregation of the MYO7A c.3696_3706del variant with the phenotype of deafness and progressive visual loss in the USH family was confirmed by Sanger sequencing...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28730277/regulation-of-class-v-myosin
#3
REVIEW
Ning Zhang, Lin-Lin Yao, Xiang-Dong Li
Class V myosin (myosin-5) is a molecular motor that functions as an organelle transporter. The activation of myosin-5's motor function has long been known to be associated with a transition from the folded conformation in the off-state to the extended conformation in the on-state, but only recently have we begun to understand the underlying mechanism. The globular tail domain (GTD) of myosin-5 has been identified as the inhibitory domain and has recently been shown to function as a dimer in regulating the motor function...
July 20, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28729432/tropomodulin1-controls-erythroblast-enucleation-via-regulation-of-f-actin-in-the-enucleosome
#4
Roberta B Nowak, Julien Papoin, David S Gokhin, Carla Casu, Stefano Rivella, Jeffrey M Lipton, Lionel Blanc, Velia M Fowler
Biogenesis of mammalian red blood cells requires nuclear expulsion by orthochromatic erythoblasts late in terminal differentiation (enucleation), but the mechanism is largely unexplained. Here, we employed high resolution confocal microscopy to analyze nuclear morphology and F-actin rearrangements during the initiation, progression and completion of mouse and human erythroblast enucleation in vivo Mouse erythroblast nuclei acquire a dumbbell-shaped morphology during enucleation, while human bone marrow erythroblast nuclei unexpectedly retain their spherical morphology...
July 20, 2017: Blood
https://www.readbyqxmd.com/read/28719725/effects-of-eupatilin-on-the-contractility-of-corpus-cavernosal-smooth-muscle-through-nitric-oxide-independent-pathways
#5
S H Choo, S W Lee, M R Chae, S J Kang, H H Sung, D H Han, J N Chun, J K Park, C Y Kim, H K Kim, I So
Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is one of the main compounds present in Artemisia species. Eupatilin has both antioxidative and anti-inflammatory properties and a relaxation effect on vascular contraction regardless of endothelial function. We evaluated the relaxant effects of eupatilin on the corpus cavernosum (CC) of rabbits and the underlying mechanisms of its activity in human corpus cavernosum smooth muscle (CCSM) cells. Isolated rabbit CC strips were mounted in an organ bath system. A conventional whole-cell patch clamp technique was used to measure activation of calcium-sensitive K(+) -channel currents in human CCSM cells...
July 18, 2017: Andrology
https://www.readbyqxmd.com/read/28717924/hypertrophic-cardiomyopathy-and-the-myosin-mesa-viewing-an-old-disease-in-a-new-light
#6
REVIEW
Darshan V Trivedi, Arjun S Adhikari, Saswata S Sarkar, Kathleen M Ruppel, James A Spudich
The sarcomere is an exquisitely designed apparatus that is capable of generating force, which in the case of the heart results in the pumping of blood throughout the body. At the molecular level, an ATP-dependent interaction of myosin with actin drives the contraction and force generation of the sarcomere. Over the past six decades, work on muscle has yielded tremendous insights into the workings of the sarcomeric system. We now stand on the cusp where the acquired knowledge of how the sarcomere contracts and how that contraction is regulated can be extended to an understanding of the molecular mechanisms of sarcomeric diseases, such as hypertrophic cardiomyopathy (HCM)...
July 17, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28716924/insights-into-the-red-algae-and-eukaryotic-evolution-from-the-genome-of-porphyra-umbilicalis-bangiophyceae-rhodophyta
#7
Susan H Brawley, Nicolas A Blouin, Elizabeth Ficko-Blean, Glen L Wheeler, Martin Lohr, Holly V Goodson, Jerry W Jenkins, Crysten E Blaby-Haas, Katherine E Helliwell, Cheong Xin Chan, Tara N Marriage, Debashish Bhattacharya, Anita S Klein, Yacine Badis, Juliet Brodie, Yuanyu Cao, Jonas Collén, Simon M Dittami, Claire M M Gachon, Beverley R Green, Steven J Karpowicz, Jay W Kim, Ulrich Johan Kudahl, Senjie Lin, Gurvan Michel, Maria Mittag, Bradley J S C Olson, Jasmyn L Pangilinan, Yi Peng, Huan Qiu, Shengqiang Shu, John T Singer, Alison G Smith, Brittany N Sprecher, Volker Wagner, Wenfei Wang, Zhi-Yong Wang, Juying Yan, Charles Yarish, Simone Zäuner-Riek, Yunyun Zhuang, Yong Zou, Erika A Lindquist, Jane Grimwood, Kerrie W Barry, Daniel S Rokhsar, Jeremy Schmutz, John W Stiller, Arthur R Grossman, Simon E Prochnik
Porphyra umbilicalis (laver) belongs to an ancient group of red algae (Bangiophyceae), is harvested for human food, and thrives in the harsh conditions of the upper intertidal zone. Here we present the 87.7-Mbp haploid Porphyra genome (65.8% G + C content, 13,125 gene loci) and elucidate traits that inform our understanding of the biology of red algae as one of the few multicellular eukaryotic lineages. Novel features of the Porphyra genome shared by other red algae relate to the cytoskeleton, calcium signaling, the cell cycle, and stress-tolerance mechanisms including photoprotection...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28715029/anisotropic-microfibrous-scaffolds-enhance-the-organization-and-function-of-cardiomyocytes-derived-from-induced-pluripotent-stem-cells
#8
Maureen Wanjare, Luqia Hou, Karina H Nakayama, Joseph J Kim, Nicholas P Mezak, Oscar J Abilez, Evangeline Tzatzalos, Joseph C Wu, Ngan F Huang
Engineering of myocardial tissue constructs is a promising approach for treatment of coronary heart disease. To engineer myocardial tissues that better mimic the highly ordered physiological arrangement and function of native cardiomyocytes, we generated electrospun microfibrous polycaprolactone scaffolds with either randomly oriented (14 μm fiber diameter) or parallel-aligned (7 μm fiber diameter) microfiber arrangement and co-seeded the scaffolds with human induced pluripotent stem cell-derived cardiomyocytes (iCMs) and endothelial cells (iECs) for up to 12 days after iCM seeding...
July 17, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28710093/the-ciliary-membrane-associated-proteome-reveals-actin-binding-proteins-as-key-components-of-cilia
#9
Priyanka Kohli, Martin Höhne, Christian Jüngst, Sabine Bertsch, Lena K Ebert, Astrid C Schauss, Thomas Benzing, Markus M Rinschen, Bernhard Schermer
Primary cilia are sensory, antennae-like organelles present on the surface of many cell types. They have been involved in a variety of diseases collectively termed ciliopathies. As cilia are essential regulators of cell signaling, the composition of the ciliary membrane needs to be strictly regulated. To understand regulatory processes at the ciliary membrane, we report the targeting of a genetically engineered enzyme specifically to the ciliary membrane to allow biotinylation and identification of the membrane-associated proteome...
July 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28701767/actomyosin-and-vimentin-cytoskeletal-networks-regulate-nuclear-shape-mechanics-and-chromatin-organization
#10
Michael C Keeling, Luis R Flores, Asad H Dodhy, Elizabeth R Murray, Núria Gavara
The regulation of nuclear state by the cytoskeleton is an important part of cellular function. Actomyosin stress fibres, microtubules and intermediate filaments have distinct and complementary roles in integrating the nucleus into its environment and influencing its mechanical state. However, the interconnectedness of cytoskeletal networks makes it difficult to dissect their individual effects on the nucleus. We use simple image analysis approaches to characterize nuclear state, estimating nuclear volume, Poisson's ratio, apparent elastic modulus and chromatin condensation...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701347/a-casein-kinase-1-prevents-expulsion-of-the-oocyte-meiotic-spindle-into-a-polar-body-by-regulating-cortical-contractility
#11
Jonathan R Flynn, Francis J McNally
During female meiosis, haploid eggs are generated from diploid oocytes. This reduction in chromosome number occurs through two highly asymmetric cell divisions resulting in one large egg and two small polar bodies. Unlike mitosis, where an actomyosin contractile ring forms between the sets of segregating chromosomes, the meiotic contractile ring forms on the cortex adjacent to one spindle pole, then ingresses down the length of the spindle to position itself at the exact midpoint between the two sets of segregating chromosomes...
July 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28701343/let-99-functions-in-the-astral-furrowing-pathway-where-it-is-required-for-myosin-enrichment-in-the-contractile-ring
#12
Kari L Price, Lesilee S Rose
The anaphase spindle determines the position of the cytokinesis furrow, such that the contractile ring assembles in an equatorial zone between the two spindle poles. Contractile ring formation is mediated by RhoA activation at the equator by the centralspindlin complex and midzone microtubules. Astral microtubules also inhibit RhoA accumulation at the poles. In the C. elegans one-cell embryo, the astral microtubule dependent pathway requires anillin, NOP-1 and LET-99. LET-99 is well characterized for generating the asymmetric cortical localization of the Gα-dependent force-generating complex that positions the spindle during asymmetric division...
July 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28700929/a-cardiomyopathy-mutation-in-the-myosin-essential-light-chain-alters-actomyosin-structure
#13
Piyali Guhathakurta, Ewa Prochniewicz, Osha Roopnarine, John A Rohde, David D Thomas
We have used site-directed time-resolved fluorescence resonance energy transfer to determine the effect of a pathological mutation in the human ventricular essential light chain (hVELC) of myosin, on the structural dynamics of the actin-myosin complex. The hVELC modulates the function of actomyosin, through the interaction of its N-terminal extension with actin and its C-terminal lobe with the myosin heavy chain. Several mutations in hVELC are associated with hypertrophic cardiomyopathy (HCM). Some biochemical effects of these mutations are known, but further insight is needed about their effects on the structural dynamics of functioning actomyosin...
July 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28699631/co-inheritance-of-mutations-associated-with-arrhythmogenic-cardiomyopathy-and-hypertrophic-cardiomyopathy
#14
Marzia De Bortoli, Chiara Calore, Alessandra Lorenzon, Martina Calore, Giulia Poloni, Elisa Mazzotti, Ilaria Rigato, Martina Perazzolo Marra, Paola Melacini, Sabino Iliceto, Gaetano Thiene, Cristina Basso, Luciano Daliento, Domenico Corrado, Alessandra Rampazzo, Barbara Bauce
Arrhythmogenic cardiomyopathy (ACM) and hypertrophic cardiomyopathy (HCM) are genetically and phenotypically distinct disorders of the myocardium. Here we describe for the first time co-inheritance of mutations in genes associated with ACM or HCM in two families with recurrence of both cardiomyopathies. Among the double heterozygotes for mutations in desmoplakin (DSP) and myosin binding protein C (MYBPC3) genes identified in Family A, two were diagnosed with ACM and two with HCM. In Family B, one patient was identified to carry mutations in α-T-catenin (CTTNA3) and β-myosin (MYH7) genes, but he does not fulfill the current diagnostic criteria neither for ACM nor for HCM...
July 12, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28687667/membrane-tension-controls-adhesion-positioning-at-the-leading-edge-of-cells
#15
Bruno Pontes, Pascale Monzo, Laurent Gole, Anabel-Lise Le Roux, Anita Joanna Kosmalska, Zhi Yang Tam, Weiwei Luo, Sophie Kan, Virgile Viasnoff, Pere Roca-Cusachs, Lisa Tucker-Kellogg, Nils C Gauthier
Cell migration is dependent on adhesion dynamics and actin cytoskeleton remodeling at the leading edge. These events may be physically constrained by the plasma membrane. Here, we show that the mechanical signal produced by an increase in plasma membrane tension triggers the positioning of new rows of adhesions at the leading edge. During protrusion, as membrane tension increases, velocity slows, and the lamellipodium buckles upward in a myosin II-independent manner. The buckling occurs between the front of the lamellipodium, where nascent adhesions are positioned in rows, and the base of the lamellipodium, where a vinculin-dependent clutch couples actin to previously positioned adhesions...
July 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28687623/nonmuscle-myosin-ii-b-regulates-epicardial-integrity-and-epicardial-derived-mesenchymal-cell-maturation
#16
Xuefei Ma, Derek C Sung, Yanqin Yang, Yoshi Wakabayashi, Robert S Adelstein
Nonmuscle myosin II-B (NMII-B) is essential for cardiac myocyte cytokinesis. The role of NMII-B in other cardiac cells is not known. Here we show that NMII-B is required in epicardial formation and function to support myocardial proliferation and coronary vessel development. Ablation of NMII-B in epicardial cells results in disruption of epicardial integrity with a loss of E-cadherin at cell-cell junctions and a focal detachment of epicardial cells from the myocardium. NMII-B ablated or blebbistatin inhibited epicardial explants demonstrate impaired mesenchymal cell maturation during epicardial epithelial-mesenchymal transition...
July 7, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28680569/ppar%C3%AE-attenuates-hypoxia-induced-hypertrophic-transcriptional-pathways-in-the-heart
#17
Abubakr Chaudhry, Kristal A Carthan, Bum-Yong Kang, John Calvert, Roy L Sutliff, C Michael Hart
Chronic hypoxia-induced pulmonary hypertension (PH) is characterized by increased pressure and resistance in the pulmonary vasculature and hypertrophy of the right ventricle (RV). The transcription factors, nuclear factor activated T-cells (NFAT), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB/p65) contribute to RV hypertrophy (RVH). Because peroxisome proliferator-activated receptor gamma (PPARγ) activation attenuates hypoxia-induced PH and RVH, we hypothesized that PPARγ inhibits activation of RV hypertrophic transcriptional signaling mechanisms...
March 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28679633/identification-of-pathogenic-gene-mutations-in-lmna-and-mybpc3-that-alter-rna-splicing
#18
Kaoru Ito, Parth N Patel, Joshua M Gorham, Barbara McDonough, Steven R DePalma, Emily E Adler, Lien Lam, Calum A MacRae, Syed M Mohiuddin, Diane Fatkin, Christine E Seidman, J G Seidman
Genetic variants that cause haploinsufficiency account for many autosomal dominant (AD) disorders. Gene-based diagnosis classifies variants that alter canonical splice signals as pathogenic, but due to imperfect understanding of RNA splice signals other variants that may create or eliminate splice sites are often clinically classified as variants of unknown significance (VUS). To improve recognition of pathogenic splice-altering variants in AD disorders, we used computational tools to prioritize VUS and developed a cell-based minigene splicing assay to confirm aberrant splicing...
July 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28679631/myosin-independent-cytokinesis-in-giardia-utilizes-flagella-to-coordinate-force-generation-and-direct-membrane-trafficking
#19
William R Hardin, Renyu Li, Jason Xu, Andrew M Shelton, Germain C M Alas, Vladimir N Minin, Alexander R Paredez
Devoid of all known canonical actin-binding proteins, the prevalent parasite Giardia lamblia uses an alternative mechanism for cytokinesis. Unique aspects of this mechanism can potentially be leveraged for therapeutic development. Here, live-cell imaging methods were developed for Giardia to establish division kinetics and the core division machinery. Surprisingly, Giardia cytokinesis occurred with a median time that is ∼60 times faster than mammalian cells. In contrast to cells that use a contractile ring, actin was not concentrated in the furrow and was not directly required for furrow progression...
July 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28671940/expanding-signaling-molecule-wavefront-model-of-cell-polarization-in-the-drosophila-wing-primordium
#20
Juliana C Wortman, Marcos Nahmad, Peng Cheng Zhang, Arthur D Lander, Clare C Yu
In developing tissues, cell polarization and proliferation are regulated by morphogens and signaling pathways. Cells throughout the Drosophila wing primordium typically show subcellular localization of the unconventional myosin Dachs on the distal side of cells (nearest the center of the disc). Dachs localization depends on the spatial distribution of bonds between the protocadherins Fat (Ft) and Dachsous (Ds), which form heterodimers between adjacent cells; and the Golgi kinase Four-jointed (Fj), which affects the binding affinities of Ft and Ds...
July 2017: PLoS Computational Biology
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