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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/28727760/detection-of-titin-fragments-in-urine-in-response-to-exercise-induced-muscle-damage
#2
Kazue Kanda, Jun Sakuma, Takayuki Akimoto, Yasuo Kawakami, Katsuhiko Suzuki
Many studies have attempted to determine the associations between blood biomarkers and exercise-induced muscle damage. However, poor correlations between the changes in biomarker levels and the magnitude of muscle symptoms have been reported. Recent advances in proteomic tools offer a strategy for the comprehensive analysis of protein expression, which can be used to identify biomarkers. Here, we used a proteomic analysis to identify urinary proteins that appear in response to a calf-raise exercise, including repetitive eccentric muscle contractions, and found that a titin (also known as connectin) N-terminal fragment molecule appears in the urine after eccentric exercise...
2017: PloS One
https://www.readbyqxmd.com/read/28724722/effect-of-directional-pulling-on-mechanical-protein-degradation-by-atp-dependent-proteolytic-machines
#3
Adrian O Olivares, Hema Chandra Kotamarthi, Benjamin J Stein, Robert T Sauer, Tania A Baker
AAA+ proteases and remodeling machines couple hydrolysis of ATP to mechanical unfolding and translocation of proteins following recognition of sequence tags called degrons. Here, we use single-molecule optical trapping to determine the mechanochemistry of two AAA+ proteases, Escherichia coli ClpXP and ClpAP, as they unfold and translocate substrates containing multiple copies of the titin(I27) domain during degradation initiated from the N terminus. Previous studies characterized degradation of related substrates with C-terminal degrons...
July 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28717163/titin-mediated-thick-filament-activation-through-a-mechanosensing-mechanism-introduces-sarcomere-length-dependencies-in-mathematical-models-of-rat-trabecula-and-whole-ventricle
#4
Lorenzo Marcucci, Takumi Washio, Toshio Yanagida
Recent experimental evidence in skeletal muscle demonstrated the existence of a thick-filament mechanosensing mechanism, acting as a second regulatory system for muscle contraction, in addition to calcium-mediated thin filament regulation. These two systems cooperate to generate force, but the extent to which their interaction is relevant in physiologically contracting muscle was not yet assessed experimentally. Therefore, we included both regulatory mechanisms in a mathematical model of rat trabecula and whole ventricle...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716623/a-second-truncation-in-ttn-causes-early-onset-recessive-muscular-dystrophy
#5
Elizabeth Harris, Ana Töpf, Anna Vihola, Anni Evilä, Rita Barresi, Judith Hudson, Peter Hackman, Brian Herron, Daniel MacArthur, Hanns Lochmüller, Kate Bushby, Bjarne Udd, Volker Straub
Mutations in the gene encoding the giant skeletal muscle protein titin are associated with a variety of muscle disorders, including recessive congenital myopathies ±cardiomyopathy, limb girdle muscular dystrophy (LGMD) and late onset dominant distal myopathy. Heterozygous truncating mutations have also been linked to dilated cardiomyopathy. The phenotypic spectrum of titinopathies is emerging and expanding, as next generation sequencing techniques make this large gene amenable to sequencing. We undertook whole exome sequencing in four individuals with LGMD...
June 22, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28712031/human-skeletal-muscle-type-1-fibre-distribution-and-response-of-stress-sensing-proteins-along-the-titin-molecule-after-submaximal-exhaustive-exercise
#6
Satu O A Koskinen, Heikki Kyröläinen, Riina Flink, Harri P Selänne, Sheila S Gagnon, Juha P Ahtiainen, Bradley C Nindl, Maarit Lehti
Early responses of stress-sensing proteins, muscle LIM protein (MLP), ankyrin repeat proteins (Ankrd1/CARP and Ankrd2/Arpp) and muscle-specific RING finger proteins (MuRF1 and MuRF2), along the titin molecule were investigated in the present experiment after submaximal exhaustive exercise. Ten healthy men performed continuous drop jumping unilaterally on a sledge apparatus with a submaximal height until complete exhaustion. Five stress-sensing proteins were analysed by mRNA measurements from biopsies obtained immediately and 3 h after the exercise from exercised vastus lateralis muscle while control biopsies were obtained from non-exercised legs before the exercise...
July 15, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28696205/increasing-evidence-of-mechanical-force-as-a-functional-regulator-in-smooth-muscle-myosin-light-chain-kinase
#7
Fabian Baumann, Magnus Sebastian Bauer, Martin Rees, Alexander Alexandrovich, Mathias Gautel, Diana Angela Pippig, Hermann Eduard Gaub
Mechanosensitive proteins are key players in cytoskeletal remodeling, muscle contraction, cell migration and differentiation processes. Smooth muscle myosin light chain kinase (smMLCK) is a member of a diverse group of serine/threonine kinases that feature cytoskeletal association. Its catalytic activity is triggered by a conformational change upon Ca(2+)/calmodulin (Ca(2+)/CaM) binding. Due to its significant homology with the force-activated titin kinase, smMLCK is suspected to be also regulatable by mechanical stress...
July 11, 2017: ELife
https://www.readbyqxmd.com/read/28676430/insulin-regulates-titin-pre-mrna-splicing-through-the-pi3k-akt-mtor-kinase-axis-in-a-rbm20-dependent-manner
#8
Chaoqun Zhu, Zhiyong Yin, Bihua Tan, Wei Guo
Titin, a giant sarcomeric protein, is largely responsible for the diastolic properties of the heart. It has two major isoforms, N2B and N2BA due to pre-mRNA splicing regulated mainly by a splicing factor RNA binding motif 20 (RBM20). Mis-splicing of titin pre-mRNA in response to external stimuli may lead to altered ratio of N2B to N2BA, and thus, impaired cardiac contractile function. However, little is known about titin alternative splicing in response to external stimuli. Here, we reported the detailed mechanisms of titin alternative splicing in response to insulin...
July 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28675036/asymmetric-conformational-transitions-in-aaa-biological-nanomachines-modulate-direction-dependent-substrate-protein-unfolding-mechanisms
#9
Abdolreza Javidialesaadi, George Stan
Powerful AAA+ biological nanomachines, such as ClpY, form hexameric ring structures, which selectively process abnormal proteins targeted for degradation by unfolding and threading them through a narrow central channel. The molecular details of this process are not yet fully understood. We perform Langevin dynamics simulations using a coarse-grained model of substrate proteins (SPs), Titin I27 and its V13P variant, threading through the ClpY pore. We probe the effect of ClpY surface heterogeneity and changes in pore width on SP orientation and the direction of applied force during SP unfolding...
July 18, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28671667/mechanochemical-evolution-of-the-giant-muscle-protein-titin-as-inferred-from-resurrected-proteins
#10
Aitor Manteca, Jörg Schönfelder, Alvaro Alonso-Caballero, Marie J Fertin, Nerea Barruetabeña, Bruna F Faria, Elias Herrero-Galán, Jorge Alegre-Cebollada, David De Sancho, Raul Perez-Jimenez
The sarcomere-based structure of muscles is conserved among vertebrates; however, vertebrate muscle physiology is extremely diverse. A molecular explanation for this diversity and its evolution has not been proposed. We use phylogenetic analyses and single-molecule force spectroscopy (smFS) to investigate the mechanochemical evolution of titin, a giant protein responsible for the elasticity of muscle filaments. We resurrect eight-domain fragments of titin corresponding to the common ancestors to mammals, sauropsids, and tetrapods, which lived 105-356 Myr ago, and compare them with titin fragments from some of their modern descendants...
July 3, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28667326/quantitative-proteomics-analysis-of-plasmodium-vivax-induced-alterations-in-human-serum-during-the-acute-and-convalescent-phases-of-infection
#11
Sandipan Ray, Sandip K Patel, Apoorva Venkatesh, Gangadhar Chatterjee, Naziya N Ansari, Nithya J Gogtay, Urmila M Thatte, Prajakta Gandhe, Santosh G Varma, Swati Patankar, Sanjeeva Srivastava
The radial distribution of Plasmodium vivax malaria burden has evoked enormous concern among the global research community. In this study, we have investigated the serum proteome alterations in non-severe vivax malaria patients before and during patient recuperation starting from the early febrile to the defervescence and convalescent stages of the infection. We have also performed an extensive quantitative proteomics analysis to compare the serum proteome profiles of vivax malaria patients with low (LPVM) and moderately-high (MPVM) parasitemia with healthy community controls...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28661225/different-amyloid-aggregation-of-smooth-muscles-titin-in-vitro
#12
Elmira I Yakupova, Ivan M Vikhlyantsev, Liya G Bobyleva, Nikita V Penkov, Alexander A Timchenko, Maria A Timchenko, Gennady A Enin, Sergei S Khutzian, Olga M Selivanova, Alexander G Bobylev
A comparative study of amyloid properties of the aggregates of smooth muscle titin (SMT) from chicken gizzard was carried out. These aggregates were formed in two solutions: 0.15 M glycine-KOH, pH 7.2-7.4 (SMT(Gly)) and 0.2 M KCl, 10 mM imidazole, pH 7.0 (SMT(KCl)). Electron microscopy data showed that SMT aggregates has an amorphous structure in both cases. The results of atomic-force microscopy demonstrated slight differences in morphology in two types of aggregates. The SMT(Gly) aggregates were represented as branching chains, composed of spherical aggregates approximately 300-500 nm in diameter and up to 35 nm in height...
June 29, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28656582/an-historical-perspective-of-the-discovery-of-titin-filaments
#13
REVIEW
Cris Dos Remedios, Darcy Gilmour
This review takes readers back to 1949, when two Australian scientists, Draper and Hodge, reported the first high-resolution electron microscopy images of striated muscle. In 1953, Jean Hanson and Hugh Huxley published phase-contrast microscopy and electron microscopy images that established the filamentous nature of the sarcomere, namely the myosin-containing thick filaments and actin-containing thin filaments. They discussed a putative third filament system, possibly a thinner actin-containing S filament, that appeared to connect one Z disc to the next...
June 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28648628/impact-of-titin-strain-on-the-cardiac-slow-force-response
#14
REVIEW
Younss Ait-Mou, Mengjie Zhang, Jody L Martin, Marion L Greaser, Pieter P de Tombe
Stretch of myocardium, such as occurs upon increased filling of the cardiac chamber, induces two distinct responses: an immediate increase in twitch force followed by a slower increase in twitch force that develops over the course of several minutes. The immediate response is due, in part, to modulation of myofilament Ca(2+) sensitivity by sarcomere length (SL). The slowly developing force response, termed the Slow Force Response (SFR), is caused by a slowly developing increase in intracellular Ca(2+) upon sustained stretch...
June 22, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28643869/mechanotransduction-properties-of-the-cytoplasmic-tail-of-pecam-1
#15
Jessica L Snyder, Elena McBeath, Tamlyn N Thomas, Yi Jen Chiu, Robert L Clark, Keigi Fujiwara
BACKGROUND: Vascular endothelial cells (ECs) are a well-known cell system used in the study of mechanobiology. Using cultured ECs, we found that platelet endothelial cell adhesion molecule 1 (PECAM-1, CD31), a cell adhesion protein localized to regions of EC-EC contact, was rapidly tyrosine phosphorylated in ECs exposed to shear or cyclic stretch. Src-homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) binds phosphorylated PECAM-1 and activates the extracellular signal-regulated kinase1/2 (ERK1/2) signaling cascade, a known flow-activated signaling pathway...
June 23, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/28642368/the-influence-of-disulfide-bonds-on-the-mechanical-stability-of-proteins-is-context-dependent
#16
Aitor Manteca, Álvaro Alonso-Caballero, Marie Fertin, Simon Poly, David De Sancho, Raul Perez-Jimenez
Disulfide bonds play a crucial role in proteins, modulating their stability and constraining their conformational dynamics. A particularly important case is that of proteins that need to withstand forces arising from their normal biological function and that are often disulfide bonded. However, the influence of disulfides on the overall mechanical stability of proteins is poorly understood. Here, we used single-molecule force spectroscopy (smFS) to study the role of disulfide bonds in different mechanical proteins in terms of their unfolding forces...
June 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28640448/overview-of-the-muscle-cytoskeleton
#17
Christine A Henderson, Christopher G Gomez, Stefanie M Novak, Lei Mi-Mi, Carol C Gregorio
Cardiac and skeletal striated muscles are intricately designed machines responsible for muscle contraction. Coordination of the basic contractile unit, the sarcomere, and the complex cytoskeletal networks are critical for contractile activity. The sarcomere is comprised of precisely organized individual filament systems that include thin (actin), thick (myosin), titin, and nebulin. Connecting the sarcomere to other organelles (e.g., mitochondria and nucleus) and serving as the scaffold to maintain cellular integrity are the intermediate filaments...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28639137/the-frank-starling-law-a-jigsaw-of-titin-proportions
#18
REVIEW
Vasco Sequeira, Jolanda van der Velden
The Frank-Starling Law dictates that the heart is able to match ejection to the dynamic changes occurring during cardiac filling, hence efficiently regulating isovolumetric contraction and shortening. In the last four decades, efforts have been made to identify a common fundamental basis for the Frank-Starling heart that can explain the direct relationship between muscle lengthening and its increased sensitization to Ca(2+). The term 'myofilament length-dependent activation' describes the length-dependent properties of the myofilaments, but what is(are) the underlying molecular mechanism(s) is a matter of ongoing debate...
June 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28637823/titin-force-enhancement-following-active-stretch-of-skinned-skeletal-muscle-fibres
#19
Krysta Powers, Venus Joumaa, Azim Jinha, Eng Kuan Moo, Ian Curtis Smith, Kiisa Nishikawa, Walter Herzog
In actively stretched skeletal muscle sarcomeres, titin-based force is enhanced, increasing the stiffness of active sarcomeres. Titin force enhancement in sarcomeres is vastly reduced in mdm, a genetic mutation with a deletion in titin. Whether loss of titin force enhancement is associated with compensatory mechanisms at higher structural levels of organization, such as single fibres or entire muscles, is unclear. The aim of this study was to determine whether mechanical deficiencies in titin force enhancement are also observed at the fibre level, and whether mechanisms compensate for the loss of titin force enhancement...
June 21, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28637492/expression-patterns-of-fshd-causing-dux4-and-myogenic-transcription-factors-pax3-and-pax7-are-spatially-distinct-in-differentiating-human-stem-cell-cultures
#20
Premi Haynes, Kelly Kernan, Suk-Lin Zhou, Daniel G Miller
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is most commonly inherited in an autosomal dominant pattern and caused by the abnormal expression of DUX4 in skeletal muscle. The DUX4 transcription factor has DNA binding domains similar to several paired class homeotic transcription factors, but only myogenic factors PAX3 and PAX7 rescue cell viability when co-expressed with DUX4 in mouse myoblasts. This observation suggests competition for DNA binding sites in satellite cells might limit muscle repair and may be one aspect of DUX4-associated myotoxicity...
June 21, 2017: Skeletal Muscle
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