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https://www.readbyqxmd.com/read/28643869/mechanotransduction-properties-of-the-cytoplasmic-tail-of-pecam-1
#1
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
#2
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
#3
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
#4
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 21, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28637823/titin-force-enhancement-following-active-stretch-of-skinned-skeletal-muscle-fibres
#5
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
#6
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
https://www.readbyqxmd.com/read/28615162/characterization-of-muscle-ankyrin-repeat-proteins-in-human-skeletal-muscle
#7
Stefan G Wette, Heather K Smith, Graham D Lamb, Robyn M Murphy
Muscle Ankyrin Repeat Proteins (MARPs) are a family of titin-associated stress response molecules and putative transducers of stretch-induced signalling in skeletal muscle. In cardiac muscle, Cardiac Ankyrin Repeat Protein (CARP) and Diabetes-Related Ankyrin Repeat Protein (DARP) reportedly redistribute from binding sites on titin to the nucleus following prolonged stretch. However, it is unclear whether Ankyrin repeat-domain protein2 (Ankrd2) shows comparable stretch-induced redistribution to the nucleus. We measured in rested human skeletal muscle 1) the absolute amount of MARPs, and 2) the distribution of Ankrd2 and DARP in both single fibers and whole muscle preparations...
June 14, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28585069/special-issue-on-titin-and-its-binding-proteins-in-striated-muscle
#8
EDITORIAL
Amy Li, Cristobal Dos Remedios
No abstract text is available yet for this article.
June 5, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28581678/ttn-genotype-is-associated-with-fascicle-length-and-marathon-running-performance
#9
Georgina K Stebbings, Alun G Williams, Adam J Herbert, Sarah J Lockey, Shane M Heffernan, Robert M Erskine, Christopher I Morse, Stephen H Day
Titin provides a molecular blueprint for muscle sarcomere assembly and sarcomere length can vary according to titin isoform expression. If variations in sarcomere length influence muscle fascicle length, this may provide an advantage for running performance. Thus the aim of this study was to investigate if the titin (TTN) rs10497520 polymorphism was associated with muscle fascicle length in recreationally active men (RA; n = 137) and marathon personal best time in male marathon runners (MR; n = 141). Fascicle length of the vastus lateralis was assessed in vivo using B-mode ultrasonography at 50% of muscle length in RA...
June 5, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28577155/rbm20-a-potential-target-for-treatment-of-cardiomyopathy-via-titin-isoform-switching
#10
REVIEW
Wei Guo, Mingming Sun
Cardiomyopathy, also known as heart muscle disease, is an unfavorable condition leading to alterations in myocardial contraction and/or impaired ability of ventricular filling. The onset and development of cardiomyopathy have not currently been well defined. Titin is a giant multifunctional sarcomeric filament protein that provides passive stiffness to cardiomyocytes and has been implicated to play an important role in the origin and development of cardiomyopathy and heart failure. Titin-based passive stiffness can be mainly adjusted by isoform switching and post-translational modifications in the spring regions...
June 2, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28555301/nuances-of-electrophoresis-study-of-titin-connectin
#11
REVIEW
Ivan M Vikhlyantsev, Zoya A Podlubnaya
Almost 40 years has passed since the discovery of giant elastic protein titin (also known as connectin) of striated and smooth muscles using gel electrophoresis. Sodium dodecyl sulfate polyacrylamide gel electrophoresis is a major technique for studying the isoform composition and content of titin. This review provides historical insights into the technical aspects of the electrophoresis methods used to identify titin and its isoforms. We particularly focus on the nuances of the technique that improve the preservation of its primary structure so that its high molecular weight isoforms can be visualized...
May 29, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28554556/dramatic-elevation-in-urinary-amino-terminal-titin-fragment-excretion-quantified-by-immunoassay-in-duchenne-muscular-dystrophy-patients-and-in-dystrophin-deficient-rodents
#12
Alan S Robertson, Mark J Majchrzak, Courtney M Smith, Robert C Gagnon, Nino Devidze, Glen B Banks, Sean C Little, Fizal Nabbie, Denise I Bounous, Janet DiPiero, Leslie K Jacobsen, Linda J Bristow, Michael K Ahlijanian, Stephen A Stimpson
Enzyme-linked and electrochemiluminescence immunoassays were developed for quantification of amino (N-) terminal fragments of the skeletal muscle protein titin (N-ter titin) and qualified for use in detection of urinary N-ter titin excretion. Urine from normal subjects contained a small but measurable level of N-ter titin (1.0 ± 0.4 ng/ml). A 365-fold increase (365.4 ± 65.0, P = 0.0001) in urinary N-ter titin excretion was seen in Duchene muscular dystrophy (DMD) patients. Urinary N-ter titin was also evaluated in dystrophin deficient rodent models...
July 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28546288/dynamic-changes-in-the-skeletal-muscle-proteome-during-denervation-induced-atrophy
#13
Franziska Lang, Sriram Aravamudhan, Hendrik Nolte, Clara Tuerk, Soraya Hölper, Stefan Müller, Stefan Günther, Bert Blaauw, Thomas Braun, Marcus Krüger
Loss of neuronal stimulation enhances protein breakdown and reduces protein synthesis, causing rapid muscle mass loss. To elucidate the pathophysiological adaptations that occur in atrophying muscles, we used stable isotope labelling and mass spectrometry to accurately quantify protein expression changes during denervation-induced atrophy after sciatic nerve section in the mouse gastrocnemius muscle (GAST). Additionally, mice were fed a SILAC diet containing (13)C6 lysine for four, seven, or eleven days to calculate relative levels of protein synthesis in denervated and control muscles...
May 25, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28539306/sarcomere-mechanics-in-striated-muscles-from-molecules-to-sarcomeres-to-cells
#14
Dilson E Rassier
Muscle contraction is commonly associated with the cross-bridge and sliding filament theories, which have received strong support from experiments conducted over the years in different laboratories. However, there are studies that cannot be readily explained by the theories, showing (i) a plateau of the force-length relation extended beyond optimal filament overlap, and forces produced at long sarcomere lengths that are higher than those predicted by the sliding filament theory, (ii) passive forces at long sarcomere lengths that can be modulated by activation and Ca(2+), which changes the force-length relation, and (iii) an unexplained high force produced during and after stretch of activated muscle fibers...
May 24, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28516329/screening-for-lipoprotein-receptor-related-protein-4-agrin-and-titin-antibodies-and-exploring-the-autoimmune-spectrum-in-myasthenia-gravis
#15
Isabell Cordts, Nicolas Bodart, Kathi Hartmann, Katerina Karagiorgou, John S Tzartos, Lin Mei, Jens Reimann, Philip Van Damme, Michael H Rivner, Alain Vigneron, Joachim Weis, Jörg B Schulz, Socrates J Tzartos, Kristl G Claeys
In autoimmune myasthenia gravis (MG), the identification of antibodies and characterization of serological subgroups is of great importance for diagnosis and management of the disease. Our aims were to study the frequency of antibodies against lipoprotein-related protein 4 (LRP4), agrin, and titin using the most recent techniques, and to characterize corresponding clinical features and autoimmune diseases (AID) in 100 MG-patients. The antibody frequencies in the 55 AChR-antibody positive patients were 7% LRP4, 5% agrin, 53% titin, and in the 45 AChR-antibody negative patients 2% MuSK, 2% LRP4, 2% agrin, and 27% titin...
June 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28510120/obscurin-variants-and-inherited-cardiomyopathies
#16
REVIEW
Steven Marston
The inherited cardiomyopathies, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and left ventricular non-compaction (LVNC), have been frequently associated with mutations in sarcomeric proteins. In recent years, advances in DNA sequencing technology has allowed the study of the giant proteins of the sarcomere, such as titin and nebulin. Obscurin has been somewhat neglected in these studies, largely because its functional role is far from clear, although there was an isolated report in 2007 of obscurin mutations associated with HCM...
May 5, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28510119/genetic-epidemiology-of-titin-truncating-variants-in-the-etiology-of-dilated-cardiomyopathy
#17
REVIEW
Ali M Tabish, Valerio Azzimato, Aris Alexiadis, Byambajav Buyandelger, Ralph Knöll
Heart failure (HF) is a complex clinical syndrome defined by the inability of the heart to pump enough blood to meet the body's metabolic demands. Major causes of HF are cardiomyopathies (diseases of the myocardium associated with mechanical and/or electrical dysfunction), among which the most common form is dilated cardiomyopathy (DCM). DCM is defined by ventricular chamber enlargement and systolic dysfunction with normal left ventricular wall thickness, which leads to progressive HF. Over 60 genes are linked to the etiology of DCM...
May 5, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28510118/tampering-with-springs-phosphorylation-of-titin-affecting-the-mechanical-function-of-cardiomyocytes
#18
REVIEW
Nazha Hamdani, Melissa Herwig, Wolfgang A Linke
Reversible post-translational modifications of various cardiac proteins regulate the mechanical properties of the cardiomyocytes and thus modulate the contractile performance of the heart. The giant protein titin forms a continuous filament network in the sarcomeres of striated muscle cells, where it determines passive tension development and modulates active contraction. These mechanical properties of titin are altered through post-translational modifications, particularly phosphorylation. Titin contains hundreds of potential phosphorylation sites, the functional relevance of which is only beginning to emerge...
April 10, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28510117/novex-3-the-tiny-titin-of-muscle
#19
REVIEW
Dalma Kellermayer, John E Smith, Henk Granzier
The giant multi-functional striated muscle protein titin is the third most abundant muscle protein after myosin and actin. Titin plays a pivotal role in myocardial passive stiffness, structural integrity and stress-initiated signaling pathways. The complete sequence of the human titin gene contains three isoform-specific mutually exclusive exons [termed novel exons (novex)] coding for the I-band sequence, named novex-1 (exon 45), novex-2 (exon 46) and novex-3 (exon 48). Transcripts containing either the novex-1 or novex-2 exons code for the novex-1 and novex-2 titin isoforms...
April 7, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28476659/effect-of-exercise-on-passive-myocardial-stiffness-in-mice-with-diastolic-dysfunction
#20
Rebecca E Slater, Joshua G Strom, Henk Granzier
Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome, characterized by increased diastolic stiffness and a preserved ejection fraction, with no effective treatment options. Here we studied the therapeutic potential of exercise for improving diastolic function in a mouse model with HFpEF-like symptoms, the TtnΔIAjxn mouse model. TtnΔIAjxn mice have increased diastolic stiffness and reduced exercise tolerance, mimicking aspects of HFpEF observed in patients. We investigated the effect of free-wheel running exercise on diastolic function...
May 3, 2017: Journal of Molecular and Cellular Cardiology
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