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Integrin talin

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https://www.readbyqxmd.com/read/28912461/vimentin-knockout-results-in-increased-expression-of-sub-endothelial-basement-membrane-components-and-carotid-stiffness-in-mice
#1
Benoit Langlois, Ekaterina Belozertseva, Ara Parlakian, Mustapha Bourhim, Jacqueline Gao-Li, Jocelyne Blanc, Lei Tian, Dario Coletti, Carlos Labat, Zhor Ramdame-Cherif, Pascal Challande, Véronique Regnault, Patrick Lacolley, Li Zhenlin
Intermediate filaments are involved in stress-related cell mechanical properties and in plasticity via the regulation of focal adhesions (FAs) and the actomyosin network. We investigated whether vimentin regulates endothelial cells (ECs) and vascular smooth muscle cells (SMCs) and thereby influences vasomotor tone and arterial stiffness. Vimentin knockout mice (Vim(-/-)) exhibited increased expression of laminin, fibronectin, perlecan, collagen IV and VE-cadherin as well as von Willebrand factor deposition in the subendothelial basement membrane...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28837696/the-macrophage-cytoskeleton-acts-as-a-contact-sensor-upon-interaction-with-entamoeba-histolytica-to-trigger-il-1%C3%AE-secretion
#2
Joëlle St-Pierre, France Moreau, Steve Cornick, Jeanie Quach, Sharmin Begum, Luz Aracely Fernandez, Hayley Gorman, Kris Chadee
Entamoeba histolytica (Eh) is the causative agent of amebiasis, one of the major causes of dysentery-related morbidity worldwide. Recent studies have underlined the importance of the intercellular junction between Eh and host cells as a determinant in the pathogenesis of amebiasis. Despite the fact that direct contact and ligation between Eh surface Gal-lectin and EhCP-A5 with macrophage α5β1 integrin are absolute requirements for NLRP3 inflammasome activation and IL-1β release, many other undefined molecular events and downstream signaling occur at the interface of Eh and macrophage...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28834730/%C3%AE-actinin-induces-a-kink-in-the-transmembrane-domain-of-%C3%AE-3-integrin-and-impairs-activation-via-talin
#3
Hengameh Shams, Mohammad R K Mofrad
Integrin-mediated signaling is crucial for cell-substrate adhesion and can be triggered from both intra- and extracellular interactions. Although talin binding is sufficient for inside-out activation of integrin, other cytoplasmic proteins such as α-actinin and filamin can directly interfere with talin-mediated integrin activation. Specifically, α-actinin plays distinct roles in regulating αIIbβ3 versus α5β1 integrin. It has been shown that α-actinin competes with talin for binding to the cytoplasmic tail of β3-integrin, whereas it cooperates with talin for activating integrin α5β1...
August 22, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28728969/a-nanoporous-titanium-surface-promotes-the-maturation-of-focal-adhesions-and-formation-of-filopodia-with-distinctive-nanoscale-protrusions-by-osteogenic-cells
#4
Dainelys Guadarrama Bello, Aurélien Fouillen, Antonella Badia, Antonio Nanci
While topography is a key determinant of the cellular response to biomaterials, the mechanisms implicated in the cell-surface interactions are complex and still not fully elucidated. In this context, we have examined the effect of nanoscale topography on the formation of filopodia, focal adhesions, and gene expression of proteins associated with cell adhesion and sensing. Commercially pure titanium discs were treated by oxidative nanopatterning with a solution of H2SO4/H2O2 50:50 (v/v). Scanning electron microscopy and atomic force microscopy characterizations showed that this facile chemical treatment efficiently creates a unique nanoporous surface with a root-mean-square roughness of 11...
July 17, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28701514/talin-the-master-of-integrin-adhesions
#5
REVIEW
Benjamin Klapholz, Nicholas H Brown
Talin has emerged as the key cytoplasmic protein that mediates integrin adhesion to the extracellular matrix. In this Review, we draw on experiments performed in mammalian cells in culture and Drosophila to present evidence that talin is the most important component of integrin adhesion complexes. We describe how the properties of this adaptor protein enable it to orchestrate integrin adhesions. Talin forms the core of integrin adhesion complexes by linking integrins directly to actin, increasing the affinity of integrin for ligands (integrin activation) and recruiting numerous proteins...
July 12, 2017: Journal of Cell Science
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
#6
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 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28695371/binding-of-%C3%AE-v%C3%AE-3-integrin-specific-radiotracers-is-modulated-by-both-integrin-expression-level-and-activation-status
#7
Alexandra Andriu, Julie Crockett, Sergio Dall'Angelo, Monica Piras, Matteo Zanda, Ian N Fleming
PURPOSE: Molecular imaging of αvβ3 integrin has exhibited real potential to guide the appropriate use of anti-angiogenic therapies. However, an incomplete understanding of the factors that influence binding of αvβ3 integrin-specific radiotracers currently limits their use for assessing response to therapy in cancer patients. This study identifies two fundamental factors that modulate uptake of these radiotracers. Procedures Experiments were performed in prostate cancer (PC3) and glioblastoma (U87MG) cells, which differentially express αvβ3 integrin...
July 10, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28652408/the-extreme-c-terminal-region-of-kindlin-2-is-critical-to-its-regulation-of-integrin-activation
#8
Jamila Hirbawi, Katarzyna Bialkowska, Kamila M Bledzka, Jianmin Liu, Koichi Fukuda, Jun Qin, Edward F Plow
Kindlin-2 (K2), a 4.1R-ezrin-radixin-moesin (FERM) domain adaptor protein, mediates numerous cellular responses, including integrin activation. The C-terminal 15-amino acid sequence of K2 is remarkably conserved across species but is absent in canonical FERM proteins, including talin. In CHO cells expressing integrin αIIbβ3, co-expression of K2 with talin head domain resulted in robust integrin activation, but this co-activation was lost after deletion of as few as seven amino acids from the K2 C terminus...
August 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28636424/fluid-shear-stress-regulates-hepg2-cell-migration-though-time-dependent-integrin-signaling-cascade
#9
Hongchi Yu, Yang Shen, Jingsi Jin, Yingying Zhang, Tang Feng, Xiaoheng Liu
Hepatocellular carcinoma (HCC) is a subtype of malignant liver cancer with poor prognosis and limited treatment options. It is noteworthy that mechanical forces in tumor microenvironment play a pivotal role in mediating the behaviors and functions of tumor cells. As an instrumental type of mechanical forces in vivo, fluid shear stress (FSS) has been reported having potent physiologic and pathologic effects on cancer progression. However, the time-dependent mechanochemical transduction in HCC induced by FSS remains unclear...
June 21, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28620171/mechanical-stability-of-talin-rod-controls-cell-migration-and-substrate-sensing
#10
Rolle Rahikainen, Magdaléna von Essen, Markus Schaefer, Lei Qi, Latifeh Azizi, Conor Kelly, Teemu O Ihalainen, Bernhard Wehrle-Haller, Martin Bastmeyer, Cai Huang, Vesa P Hytönen
Cells adhere to the surrounding tissue and probe its mechanical properties by forming cell-matrix adhesions. Talin is a critical adhesion protein and participates in the transmission of mechanical signals between extracellular matrix and cell cytoskeleton. Force induced unfolding of talin rod subdomains has been proposed to act as a cellular mechanosensor, but so far evidence linking their mechanical stability and cellular response has been lacking. Here, by utilizing computationally designed mutations, we demonstrate that stepwise destabilization of the talin rod R3 subdomain decreases cellular traction force generation, which affects talin and vinculin dynamics in cell-matrix adhesions and results in the formation of talin-rich but unstable adhesions...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611383/integrin-%C3%AE-2%C3%AE-1-in-nonactivated-conformation-can-induce-focal-adhesion-kinase-signaling
#11
Maria Salmela, Johanna Jokinen, Silja Tiitta, Pekka Rappu, R Holland Cheng, Jyrki Heino
Conformational activation of integrins is generally required for ligand binding and cellular signalling. However, we have previously reported that the nonactivated conformation of α2β1 integrin can also bind to large ligands, such as human echovirus 1. In this study, we show that the interaction between the nonactivated integrin and a ligand resulted in the activation of focal adhesion kinase (FAK) in a protein kinase C dependent manner. A loss-of-function mutation, α2E336A, in the α2-integrin did not prevent the activation of FAK, nor did EDTA-mediated inactivation of the integrin...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515282/talin-plays-a-critical-role-in-the-maintenance-of-the-regulatory-t-cell-pool
#12
Jane E Klann, Kelly A Remedios, Stephanie H Kim, Patrick J Metz, Justine Lopez, Lauren A Mack, Ye Zheng, Mark H Ginsberg, Brian G Petrich, John T Chang
Talin, a cytoskeletal protein essential in mediating integrin activation, has been previously shown to be involved in the regulation of T cell proliferation and function. In this study, we describe a role for talin in maintaining the homeostasis and survival of the regulatory T (Treg) cell pool. T cell-specific deletion of talin in Tln1(fl/fl)Cd4(Cre) mice resulted in spontaneous lymphocyte activation, primarily due to numerical and functional deficiencies of Treg cells in the periphery. Peripheral talin-deficient Treg cells were unable to maintain high expression of IL-2Rα, resulting in impaired IL-2 signaling and ultimately leading to increased apoptosis through downregulation of prosurvival proteins Bcl-2 and Mcl-1...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28487468/epigallocatechin-gallate-has-pleiotropic-effects-on-transmembrane-signaling-by-altering-the-embedding-of-transmembrane-domains
#13
Feng Ye, Chansik Yang, Jiyoon Kim, Christopher J MacNevin, Klaus M Hahn, Dongeun Park, Mark H Ginsberg, Chungho Kim
Epigallocatechin gallate (EGCG) is the principal bioactive ingredient in green tea and has been reported to have many health benefits. EGCG influences multiple signal transduction pathways related to human diseases, including redox, inflammation, cell cycle, and cell adhesion pathways. However, the molecular mechanisms of these varying effects are unclear, limiting further development and utilization of EGCG as a pharmaceutical compound. Here, we examined the effect of EGCG on two representative transmembrane signaling receptors, integrinαIIbβ3 and epidermal growth factor receptor (EGFR)...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28432753/identification-of-indothiazinone-as-a-natural-antiplatelet-agent
#14
Chansik Yang, Sugyeong Kwon, Se-Jong Kim, Minseon Jeong, Ji-Young Park, Dongeun Park, Soon Jun Hong, Jong-Wha Jung, Chungho Kim
Cardiovascular disease, which is caused by unregulated platelet aggregation, is one of the main causes of deaths worldwide. Many studies have focused on natural products with antiplatelet effects as a safe alternative therapy to prevent the disease. In this context, an in-house chemical library was screened to find natural products capable of inhibiting the interaction between platelet integrin αIIbβ3 and fibrinogen, which is an essential step in platelet aggregation. On the basis of the screening results, indothiazinone, an alkaloid found in microbial cultures, was identified as a potential antiplatelet agent...
April 22, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28428266/kca1-1-channels-regulate-%C3%AE-1-integrin-function-and-cell-adhesion-in-rheumatoid-arthritis-fibroblast-like-synoviocytes
#15
Mark R Tanner, Michael W Pennington, Teresina Laragione, Pércio S Gulko, Christine Beeton
Large-conductance calcium-activated potassium channel (KCa1.1; BK, Slo1, MaxiK, KCNMA1) is the predominant potassium channel expressed at the plasma membrane of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) isolated from the synovium of patients with RA. It is a critical regulator of RA-FLS migration and invasion and therefore represents an attractive target for the therapy of RA. However, the molecular mechanisms by which KCa1.1 regulates RA-FLS invasiveness have remained largely unknown. Here, we demonstrate that KCa1...
August 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28428218/gain-of-function-mutation-in-filamin-a-potentiates-platelet-integrin-%C3%AE-iib%C3%AE-3-activation
#16
Eliane Berrou, Frédéric Adam, Marilyne Lebret, Virginie Planche, Patricia Fergelot, Odile Issertial, Isabelle Coupry, Jean-Claude Bordet, Paquita Nurden, Dominique Bonneau, Estelle Colin, Cyril Goizet, Jean-Philippe Rosa, Marijke Bryckaert
OBJECTIVE: Dominant mutations of the X-linked filamin A (FLNA) gene are responsible for filaminopathies A, which are rare disorders including brain periventricular nodular heterotopia, congenital intestinal pseudo-obstruction, cardiac valves or skeleton malformations, and often macrothrombocytopenia. APPROACH AND RESULTS: We studied a male patient with periventricular nodular heterotopia and congenital intestinal pseudo-obstruction, his unique X-linked FLNA allele carrying a stop codon mutation resulting in a 100-amino acid-long FLNa C-terminal extension (NP_001447...
June 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28428216/maturation-of-platelet-function-during-murine-fetal-development-in-vivo
#17
COMPARATIVE STUDY
Andreas Margraf, Claudia Nussbaum, Ina Rohwedder, Sarah Klapproth, Angela R M Kurz, Annamaria Florian, Volker Wiebking, Joachim Pircher, Monika Pruenster, Roland Immler, Steffen Dietzel, Ludmila Kremer, Friedemann Kiefer, Markus Moser, Andreas W Flemmer, Elizabeth Quackenbush, Ulrich H von Andrian, Markus Sperandio
OBJECTIVE: Platelet function has been intensively studied in the adult organism. However, little is known about the function and hemostatic capacity of platelets in the developing fetus as suitable in vivo models are lacking. APPROACH AND RESULTS: To examine fetal platelet function in vivo, we generated a fetal thrombosis model and investigated light/dye-induced thrombus formation by intravital microscopy throughout gestation. We observed that significantly less and unstable thrombi were formed at embryonic day (E) 13...
June 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28408404/smurf1-inhibits-integrin-activation-by-controlling-kindlin-2-ubiquitination-and-degradation
#18
Xiaofan Wei, Xiang Wang, Jun Zhan, Yuhan Chen, Weigang Fang, Lingqiang Zhang, Hongquan Zhang
Integrin activation is an indispensable step for various integrin-mediated biological functions. Kindlin-2 is known to coactivate integrins with Talin; however, molecules that restrict integrin activation are elusive. Here, we demonstrate that the E3 ubiquitin ligase Smurf1 controls the amount of Kindlin-2 protein in cells and hinders integrin activation. Smurf1 interacts with and promotes Kindlin-2 ubiquitination and degradation. Smurf1 selectively mediates degradation of Kindlin-2 but not Talin, leading to inhibition of αIIbβ3 integrin activation in Chinese hamster ovary cells and β1 integrin activation in fibroblasts...
May 1, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28361943/talin-gets-shanked-in-the-fight-for-integrin-activation
#19
Paul Atherton, Christoph Ballestrem
Genetic mutations in the SHANK family of proteins are linked to multiple neuropsychiatric disorders including autism spectrum disorders. A study now elucidates critical roles for SHANK in regulating integrin-mediated cell-extracellular matrix adhesion, by sequestering integrin activators.
March 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28351192/synergistic-effect-of-peptide-inhibitors-derived-from-the-extracellular-and-intracellular-domain-of-%C3%AE-iib-subunit-of-integrin-%C3%AE-iib%C3%AE-3-on-platelet-activation-and-aggregation
#20
Alexia V Gkourogianni, Klytaimnistra Kiouptsi, Vassiliki Koloka, Vassilios Moussis, Vassilios Tsikaris, Christilla Bachelot-Loza, Demokritos C Tsoukatos
αIIbβ3, the major platelet integrin, plays a central role in hemostasis and thrombosis. Upon platelet activation, conformation of αIIbβ3 changes and allows fibrinogen binding and, subsequently, platelet aggregation. It was previously shown that a lipid-modified platelet permeable peptide, which corresponds to the intracellular acidic membrane distal sequence (1000)LEEDDEEGE(1008) of αIIb (pal-K-LEEDDEEGE or pal-K-1000-1008), inhibits thrombin-induced human platelet aggregation, by inhibiting talin association with the integrin...
March 29, 2017: Platelets
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