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https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#1
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
July 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28724775/n-degradomic-analysis-reveals-a-proteolytic-network-processing-the-podocyte-cytoskeleton
#2
Markus M Rinschen, Ann-Kathrin Hoppe, Florian Grahammer, Martin Kann, Linus A Völker, Eva-Maria Schurek, Julie Binz, Martin Höhne, Fatih Demir, Milena Malisic, Tobias B Huber, Christine Kurschat, Jayachandran N Kizhakkedathu, Bernhard Schermer, Pitter F Huesgen, Thomas Benzing
Regulated intracellular proteostasis, controlled in part by proteolysis, is essential in maintaining the integrity of podocytes and the glomerular filtration barrier of the kidney. We applied a novel proteomics technology that enables proteome-wide identification, mapping, and quantification of protein N-termini to comprehensively characterize cleaved podocyte proteins in the glomerulus in vivo We found evidence that defined proteolytic cleavage results in various proteoforms of important podocyte proteins, including those of podocin, nephrin, neph1, α-actinin-4, and vimentin...
July 19, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28720718/phosphorylation-of-amyloid-precursor-protein-by-mutant-lrrk2-promotes-aicd-activity-and-neurotoxicity-in-parkinson-s-disease
#3
Zhong-Can Chen, Wei Zhang, Ling-Ling Chua, Chou Chai, Rong Li, Lin Lin, Zhen Cao, Dario C Angeles, Lawrence W Stanton, Jian-He Peng, Zhi-Dong Zhou, Kah-Leong Lim, Li Zeng, Eng-King Tan
Mutations in LRRK2, which encodes leucine-rich repeat kinase 2, are the most common genetic cause of familial and sporadic Parkinson's disease (PD), a degenerative disease of the central nervous system that causes impaired motor function and, in advanced stages, dementia. Dementia is a common symptom of another neurodegenerative disease, Alzheimer's disease, and research suggests that there may be pathophysiological and genetic links between the two diseases. Aggregates of β amyloid [a protein produced through cleavage of amyloid precursor protein (APP)] are seen in both diseases and in PD patients carrying G2019S-mutant LRRK2...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28719319/phosphoproteome-of-toxoplasma-gondii-infected-host-cells-reveals-specific-cellular-processes-predominating-in-different-phases-of-infection
#4
Cheng He, Ai-Yuan Chen, Hai-Xia Wei, Xiao-Shuang Feng, Hong-Juan Peng
The invasion of Toxoplasma gondii tachyzoites into the host cell results in extensive host cell signaling activation/deactivation that is usually regulated by the phosphorylation/dephosphorylation. To elucidate how T. gondii regulates host cell signal transduction, the comparative phosphoproteome of stable isotope labeling with amino acids in cell culture-labeled human foreskin fibroblast cells was analyzed. The cells were grouped (Light [L], Medium [M], and Heavy [H] groups) based on the labeling isotope weight and were infected with T...
July 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28717253/prostacyclin-reverses-platelet-stress-fibre-formation-causing-platelet-aggregate-instability
#5
M Z Yusuf, Z Raslan, L Atkinson, A Aburima, S G Thomas, K M Naseem, S D J Calaminus
Prostacyclin (PGI2) modulates platelet activation to regulate haemostasis. Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation. It was hypothesised that PGI2 could reverse platelet spreading by actin cytoskeletal modulation, leading to reduced capability of platelet aggregates to withstand a high shear environment. Our data demonstrates that post-flow of PGI2 over activated and spread platelets on fibrinogen, identified a significant reduction in platelet surface area under high shear...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715434/engineered-extracellular-matrices-with-controlled-mechanics-modulate-renal-proximal-tubular-cell-epithelialization
#6
Jeffrey A Beamish, Evan Chen, Andrew J Putnam
Acute kidney injury (AKI) is common and associated with significant morbidity and mortality. Recovery from many forms of AKI involves the proliferation of renal proximal tubular epithelial cells (RPTECs), but the influence of the microenvironment in which this recovery occurs remains poorly understood. Here we report the development of a poly(ethylene glycol) (PEG) hydrogel platform to study the influence of substrate mechanical properties on the proliferation of human RPTECs as a model for recovery from AKI...
2017: PloS One
https://www.readbyqxmd.com/read/28714568/exposure-to-reversine-affects-the-chondrocyte-morphology-and-phenotype-in-vitro
#7
S Gasparini, F Villa, L Molfetta, E Repaci, P Castagnola, R Quarto, P Giannoni
Articular chondrocytes derived from osteoarthritic tissues (OA-HAC) show a severely reduced chondrogenic commitment. This impairment undermines their use for tissue-engineered cartilage repair, which relies on cell proliferation and growth to meet the therapeutic needs but also on efficient cell plasticity to recover the chondrogenic phenotype. Reversine (Rev), a 2,6-disubstituted purine inhibitor of spindle-assembly checkpoints, was described to convert differentiated mesenchymal cells to their undifferentiated precursors...
July 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28713489/the-inhibitory-effect-of-wenxinkeli-on-h9c2-cardiomyocytes-hypertrophy-induced-by-angiotensin-ii-through-regulating-autophagy-activity
#8
Jie Li, Yang Li, Ying Zhang, Dan Hu, Yonghong Gao, Hongcai Shang, Yanwei Xing
OBJECTIVES: We investigated the role of cardiomyocyte autophagy and its regulatory mechanisms by WenxinKeli (WXKL) in cells subjected to hypertrophy. METHODS: H9C2 cardiomyocytes were divided into 8 groups. Cytoskeletal proteins as well as endogenously expressed autophagy marker proteins were studied by confocal imaging. Western blotting was used to assess the levels of light chain-3 (LC3) and mechanistic target of rapamycin (mTOR). The cell viability assay was used to detect the content of ATP...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28711718/phospholipase-d1-is-a-regulator-of-platelet-mediated-inflammation
#9
Meike Klier, Nina Sarah Gowert, Sven Jäckel, Christoph Reinhardt, Margitta Elvers
Glycoprotein (GP)Ib is not only required for stable thrombus formation but for platelet-mediated inflammatory responses. Phospholipase (PL)D1 is essential for GPIb-dependent aggregate formation under high shear conditions while nothing is known about PLD1-induced regulation of GPIb in platelet-mediated inflammation and the underlying mechanisms. This study aimed to investigate the relevance of PLD1 for platelet-mediated endothelial and leukocyte recruitment and activation in vitro and in vivo. Pld1(-/-) platelets showed strongly reduced adhesion to TNFα stimulated endothelial cells (ECs) under high shear conditions ex vivo...
July 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28701483/the-shigella-type-iii-effector-ipgd-recodes-ca-2-signals-during-invasion-of-epithelial-cells
#10
Chun Hui Sun, Benjamin Wacquier, Daniel I Aguilar, Nathalie Carayol, Kevin Denis, Sylviane Boucherie, Cesar Valencia-Gallardo, Ceren Simsek, Christophe Erneux, Alexandre Lehman, Jost Enninga, Laurence Arbibe, Philippe Sansonetti, Geneviève Dupont, Laurent Combettes, Guy Tran Van Nhieu
The role of second messengers in the diversion of cellular processes by pathogens remains poorly studied despite their importance. Among these, Ca(2+) virtually regulates all known cell processes, including cytoskeletal reorganization, inflammation, or cell death pathways. Under physiological conditions, cytosolic Ca(2+) increases are transient and oscillatory, defining the so-called Ca(2+) code that links cell responses to specific Ca(2+) oscillatory patterns. During cell invasion, Shigella induces atypical local and global Ca(2+) signals...
July 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28698364/loss-of-mouse-cardiomyocyte-talin-1-and-talin-2-leads-to-%C3%AE-1-integrin-reduction-costameric-instability-and-dilated-cardiomyopathy
#11
Ana Maria Manso, Hideshi Okada, Francesca M Sakamoto, Emily Moreno, Susan J Monkley, Ruixia Li, David R Critchley, Robert S Ross
Continuous contraction-relaxation cycles of the heart require strong and stable connections of cardiac myocytes (CMs) with the extracellular matrix (ECM) to preserve sarcolemmal integrity. CM attachment to the ECM is mediated by integrin complexes localized at the muscle adhesion sites termed costameres. The ubiquitously expressed cytoskeletal protein talin (Tln) is a component of muscle costameres that links integrins ultimately to the sarcomere. There are two talin genes, Tln1 and Tln2. Here, we tested the function of these two Tln forms in myocardium where Tln2 is the dominant isoform in postnatal CMs...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28697804/ang-ii-at2r-increases-mesenchymal-stem-cell-migration-by-signaling-through-the-fak-and-rhoa-cdc42-pathways-in-vitro
#12
Xiu-Ping Xu, Hong-Li He, Shu-Ling Hu, Ji-Bin Han, Li-Li Huang, Jing-Yuan Xu, Jian-Feng Xie, Ai-Ran Liu, Yi Yang, Hai-Bo Qiu
BACKGROUND: Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury and are possibly attracted by inflammatory factors. As a proinflammatory mediator, angiotensin II (Ang II) reportedly enhances the migration of various cell types by signaling via the Ang II receptor in vitro. However, few studies have focused on the effects of Ang II on MSC migration and the underlying mechanisms. METHODS: Human bone marrow MSCs migration was measured using wound healing and Boyden chamber migration assays after treatments with different concentrations of Ang II, an AT1R antagonist (Losartan), and/or an AT2R antagonist (PD-123319)...
July 12, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28696205/increasing-evidence-of-mechanical-force-as-a-functional-regulator-in-smooth-muscle-myosin-light-chain-kinase
#13
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/28690317/cytoskeletal-control-of-b-cell-responses-to-antigens
#14
REVIEW
Pavel Tolar
The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton is extensively coupled to B cell receptor (BCR) signalling pathways, and defects of the actin cytoskeleton can either promote or suppress B cell activation. Recent insights from studies using single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion and that it regulates antigen discrimination through the biomechanics of immune synapses...
July 10, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28687623/nonmuscle-myosin-ii-b-regulates-epicardial-integrity-and-epicardial-derived-mesenchymal-cell-maturation
#15
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/28686848/transcriptional-regulation-of-endmt-in-cardiac-fibrosis-role-of-mrtf-a-and-atf3
#16
Vibhuti Sharma, Nilambra Dogra, Uma Saikia, Madhu Khullar
The etiology of cardiac fibrogenesis is quite diverse but a common feature is the presence of activated fibroblasts. Experimental evidence suggests that a subset of cardiac fibroblasts is derived via transition of vascular endothelial cells into fibroblasts by endothelial to mesenchymal transition (EndMT). During EndMT, endothelial cells lose their endothelial characteristics and acquire a mesenchymal phenotype. Molecular mechanisms and the transcriptional mediators controlling EndMT in heart during development or disease remain relatively undefined...
July 7, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28680579/the-arp-2-3-complex-mediates-endothelial-barrier-function-and-recovery
#17
Patrick Belvitch, Mary E Brown, Brittany N Brinley, Eleftheria Letsiou, Alicia N Rizzo, Joe G N Garcia, Steven M Dudek
Pulmonary endothelial cell (EC) barrier dysfunction and recovery is critical to the pathophysiology of acute respiratory distress syndrome. Cytoskeletal and subsequent cell membrane dynamics play a key mechanistic role in determination of EC barrier integrity. Here, we characterizAQe the actin related protein 2/3 (Arp 2/3) complex, a regulator of peripheral branched actin polymerization, in human pulmonary EC barrier function through studies of transendothelial electrical resistance (TER), intercellular gap formation, peripheral cytoskeletal structures and lamellipodia...
March 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28679962/fibroblast-deletion-of-rock2-attenuates-cardiac-hypertrophy-fibrosis-and-diastolic-dysfunction
#18
Toru Shimizu, Nikhil Narang, Phetcharat Chen, Brian Yu, Maura Knapp, Jyothi Janardanan, John Blair, James K Liao
Although left ventricular (LV) diastolic dysfunction is often associated with hypertension, little is known regarding its underlying pathophysiological mechanism. Here, we show that the actin cytoskeletal regulator, Rho-associated coiled-coil containing kinase-2 (ROCK2), is a critical mediator of LV diastolic dysfunction. In response to angiotensin II (Ang II), mutant mice with fibroblast-specific deletion of ROCK2 (ROCK2Postn-/-) developed less LV wall thickness and fibrosis, along with improved isovolumetric relaxation...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28679472/nkcc1-regulates-migration-ability-of-glioblastoma-cells-by-modulation-of-actin-dynamics-and-interacting-with-cofilin
#19
Paula Schiapparelli, Hugo Guerrero-Cazares, Roxana Magaña-Maldonado, Susan M Hamilla, Sara Ganaha, Eric Goulin Lippi Fernandes, Chuan-Hsiang Huang, Helim Aranda-Espinoza, Peter Devreotes, Alfredo Quinones-Hinojosa
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. The mechanisms that confer GBM cells their invasive behavior are poorly understood. The electroneutral Na(+)-K(+)-2Cl(-) co-transporter 1 (NKCC1) is an important cell volume regulator that participates in cell migration. We have shown that inhibition of NKCC1 in GBM cells leads to decreased cell migration, in vitro and in vivo. We now report on the role of NKCC1 on cytoskeletal dynamics. We show that GBM cells display a significant decrease in F-actin content upon NKCC1 knockdown (NKCC1-KD)...
June 21, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28678601/adhesion-structures-in-leukemia-cells-and-their-regulation-by-src-family-kinases
#20
Pavla Röselová, Adam Obr, Aleš Holoubek, Dana Grebeňová, Kateřina Kuželová
Interaction of leukemia blasts with the bone marrow extracellular matrix often results in protection of leukemia cells from chemotherapy and in persistence of the residual disease which is on the basis of subsequent relapses. The adhesion signaling pathways have been extensively studied in adherent cells as well as in mature hematopoietic cells, but the adhesion structures and signaling in hematopoietic stem and progenitor cells, either normal or malignant, are much less explored. We analyzed the interaction of leukemia cells with fibronectin (FN) using interference reflection microscopy, immunofluorescence, measurement of adherent cell fraction, real-time microimpedance measurement and live cell imaging...
July 5, 2017: Cell Adhesion & Migration
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