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Integrin talin

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https://www.readbyqxmd.com/read/29141864/il-1%C3%AE-induces-pathologically-activated-osteoclasts-bearing-extremely-high-levels-of-resorbing-activity-a-possible-pathological-subpopulation-of-osteoclasts-accompanied-by-suppressed-expression-of-kindlin-3-and-talin-1
#1
Takuma Shiratori, Yukari Kyumoto-Nakamura, Akiko Kukita, Norihisa Uehara, Jingqi Zhang, Kinuko Koda, Mako Kamiya, Tamer Badawy, Erika Tomoda, Xianghe Xu, Takayoshi Yamaza, Yasuteru Urano, Kiyoshi Koyano, Toshio Kukita
As osteoclasts have the central roles in normal bone remodeling, it is ideal to regulate only the osteoclasts performing pathological bone destruction without affecting normal osteoclasts. Based on a hypothesis that pathological osteoclasts form under the pathological microenvironment of the bone tissues, we here set up optimum culture conditions to examine the entity of pathologically activated osteoclasts (PAOCs). Through searching various inflammatory cytokines and their combinations, we found the highest resorbing activity of osteoclasts when osteoclasts were formed in the presence of M-CSF, receptor activator of NF-κB ligand, and IL-1β...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29115292/fibronectin-bound-%C3%AE-5%C3%AE-1-integrins-sense-load-and-signal-to-reinforce-adhesion-in-less-than-a-second
#2
Nico Strohmeyer, Mitasha Bharadwaj, Mercedes Costell, Reinhard Fässler, Daniel J Müller
Integrin-mediated mechanosensing of the extracellular environment allows cells to control adhesion and signalling. Whether cells sense and respond to force immediately upon ligand-binding is unknown. Here, we report that during adhesion initiation, fibroblasts respond to mechanical load by strengthening integrin-mediated adhesion to fibronectin (FN) in a biphasic manner. In the first phase, which depends on talin and kindlin as well as on the actin nucleators Arp2/3 and mDia, FN-engaged α5β1 integrins activate focal adhesion kinase (FAK) and c-Src in less than 0...
November 6, 2017: Nature Materials
https://www.readbyqxmd.com/read/29073038/actin-retrograde-flow-actively-aligns-and-orients-ligand-engaged-integrins-in-focal-adhesions
#3
Vinay Swaminathan, Joseph Mathew Kalappurakkal, Shalin B Mehta, Pontus Nordenfelt, Travis I Moore, Nobuyasu Koga, David A Baker, Rudolf Oldenbourg, Tomomi Tani, Satyajit Mayor, Timothy A Springer, Clare M Waterman
Integrins are transmembrane receptors that, upon activation, bind extracellular ligands and link them to the actin filament (F-actin) cytoskeleton to mediate cell adhesion and migration. Cytoskeletal forces in migrating cells generated by polymerization- or contractility-driven "retrograde flow" of F-actin from the cell leading edge have been hypothesized to mediate integrin activation for ligand binding. This predicts that these forces should align and orient activated, ligand-bound integrins at the leading edge...
October 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29069646/the-intracranial-aneurysm-gene-thsd1-connects-endosome-dynamics-to-nascent-focal-adhesion-assembly
#4
Yan-Ning Rui, Zhen Xu, Xiaoqian Fang, Miriam R Menezes, Julien Balzeau, Airu Niu, John P Hagan, Dong H Kim
BACKGROUND/AIMS: We recently discovered that harmful variants in THSD1 (Thrombospondin type-1 domain-containing protein 1) likely cause intracranial aneurysm and subarachnoid hemorrhage in a subset of both familial and sporadic patients with supporting evidence from two vertebrate models. The current study seeks to elucidate how THSD1 and patient-identified variants function molecularly in focal adhesions. METHODS: Co-immunostaining and co-immunoprecipitation were performed to define THSD1 subcellular localization and interacting partners...
October 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28993400/talin-regulates-integrin-%C3%AE-1-dependent-and-independent-cell-functions-in-ureteric-bud-development
#5
Sijo Mathew, Riya J Palamuttam, Glenda Mernaugh, Harini Ramalingam, Zhenwei Lu, Ming-Zhi Zhang, Shuta Ishibe, David R Critchley, Reinhard Fässler, Ambra Pozzi, Charles R Sanders, Thomas J Carroll, Roy Zent
Kidney collecting system development requires integrin-dependent cell-extracellular matrix interactions. Integrins, are heterodimeric transmembrane receptors consisting of α and β subunits and critical integrins in the kidney collecting system express the β1subunit. The β1 cytoplasmic tail has two NPxY motifs that mediate functions by binding to cytoplasmic signaling and scaffolding molecules. Talins, scaffolding proteins that bind to the membrane proximal NPxY motif, are proposed to activate integrins and link them to the actin cytoskeleton...
October 9, 2017: Development
https://www.readbyqxmd.com/read/28954813/kindlin-supports-platelet-integrin-%C3%AE-iib%C3%AE-3-activation-by-interacting-with-paxillin
#6
Juan Gao, Ming Huang, Jingjing Lai, Kaijun Mao, Peisen Sun, Zhongyuan Cao, Youpei Hu, Yingying Zhang, Marie L Schulte, Chaozhi Jin, Jian Wang, Gilbert C White, Zhen Xu, Yan-Qing Ma
Kindlins play an important role in supporting integrin activation by cooperating with talin; however, the mechanistic details remain unclear. Here, we disclosed that kindlins directly interacted with paxillin and this interaction could support integrin αIIbβ3 activation. An exposed loop in the N-terminal F0 subdomain of kindlins was involved in mediating the interaction. Disruption of kindlin binding to paxillin by structure-based mutations significantly impaired the function of kindlins in supporting integrin αIIbβ3 activation...
September 27, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28945706/multiplexing-molecular-tension-sensors-reveals-piconewton-force-gradient-across-talin-1
#7
Pia Ringer, Andreas Weißl, Anna-Lena Cost, Andrea Freikamp, Benedikt Sabass, Alexander Mehlich, Marc Tramier, Matthias Rief, Carsten Grashoff
Förster resonance energy transfer (FRET)-based tension sensor modules (TSMs) are available for investigating how distinct proteins bear mechanical forces in cells. Yet, forces in the single piconewton (pN) regime remain difficult to resolve, and tools for multiplexed tension sensing are lacking. Here, we report the generation and calibration of a genetically encoded, FRET-based biosensor called FL-TSM, which is characterized by a near-digital force response and increased sensitivity at 3-5 pN. In addition, we present a method allowing the simultaneous evaluation of coexpressed tension sensor constructs using two-color fluorescence lifetime microscopy...
November 2017: Nature Methods
https://www.readbyqxmd.com/read/28912461/vimentin-knockout-results-in-increased-expression-of-sub-endothelial-basement-membrane-components-and-carotid-stiffness-in-mice
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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