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Integrin talin

Hao Sun, Frederic Lagarrigue, Alexandre R Gingras, Zhichao Fan, Klaus Ley, Mark H Ginsberg
Integrin activation regulates adhesion, extracellular matrix assembly, and cell migration, thereby playing an indispensable role in development and in many pathological processes. A proline mutation in the central integrin β3 transmembrane domain (TMD) creates a flexible kink that uncouples the topology of the inner half of the TMD from the outer half. In this study, using leukocyte integrin α4β7, which enables development of gut-associated lymphoid tissue (GALT), we examined the biological effect of such a proline mutation and report that it impairs agonist-induced talin-mediated activation of integrin α4β7, thereby inhibiting rolling lymphocyte arrest, a key step in transmigration...
March 13, 2018: Journal of Cell Biology
Elias H Barriga, Kristian Franze, Guillaume Charras, Roberto Mayor
Collective cell migration is essential for morphogenesis, tissue remodelling and cancer invasion. In vivo, groups of cells move in an orchestrated way through tissues. This movement involves mechanical as well as molecular interactions between cells and their environment. While the role of molecular signals in collective cell migration is comparatively well understood, how tissue mechanics influence collective cell migration in vivo remains unknown. Here we investigated the importance of mechanical cues in the collective migration of the Xenopus laevis neural crest cells, an embryonic cell population whose migratory behaviour has been likened to cancer invasion...
February 14, 2018: Nature
Dror S Chorev, Tova Volberg, Ariel Livne, Miriam Eisenstein, Bruno Martins, Zvi Kam, Brigitte M Jockusch, Ohad Medalia, Michal Sharon, Benny Geiger
Focal adhesions (FAs) are multi-protein complexes that connect the actin cytoskeleton to the extracellular matrix, via integrin receptors. The growth, stability and adhesive functionality of these structures are tightly regulated by mechanical stress, yet, despite the extensive characterization of the integrin adhesome, the detailed molecular mechanisms underlying FA mechanosensitivity are still unclear. Besides talin, another key candidate for regulating FA-associated mechanosensing, is vinculin, a prominent FA component, which possesses either closed ("auto-inhibited") or open ("active") conformation...
February 9, 2018: Scientific Reports
Katarzyna I Jankowska, Edward K Williamson, Nathan H Roy, Daniel Blumenthal, Vidhi Chandra, Tobias Baumgart, Janis K Burkhardt
Full T cell activation requires coordination of signals from multiple receptor-ligand pairs that interact in parallel at a specialized cell-cell contact site termed the immunological synapse (IS). Signaling at the IS is intimately associated with actin dynamics; T cell receptor (TCR) engagement induces centripetal flow of the T cell actin network, which in turn enhances the function of ligand-bound integrins by promoting conformational change. Here, we have investigated the effects of integrin engagement on actin flow, and on associated signaling events downstream of the TCR...
2018: Frontiers in Immunology
Mark Bennett, Marco Cantini, Julien Reboud, Jonathan M Cooper, Pere Roca-Cusachs, Manuel Salmeron-Sanchez
Cell response to matrix rigidity has been explained by the mechanical properties of the actin-talin-integrin-fibronectin clutch. Here the molecular clutch model is extended to account for cell interactions with purely viscous surfaces (i.e., without an elastic component). Supported lipid bilayers present an idealized and controllable system through which to study this concept. Using lipids of different diffusion coefficients, the mobility (i.e., surface viscosity) of the presented ligands (in this case RGD) was altered by an order of magnitude...
January 22, 2018: Proceedings of the National Academy of Sciences of the United States of America
Sebastian Blatt, Andreas Max Pabst, Eik Schiegnitz, Marco Hosang, Thomas Ziebart, Christian Walter, Bilal Al-Nawas, Marcus Oliver Klein
OBJECTIVES: Osseointegration of dental implants is a crucial prerequisite for long-term survival. Therefore, surface modifications are needed to interact with the extracellular environment and to trigger osteogenic cell responses such as cell proliferation, adherence, and differentiation. The purpose of this study was to investigate different surface modifications in vitro over 2 weeks. MATERIALS AND METHODS: Commercially available cells from a human osteogenic cell line (HHOB-c) were cultivated on the following surfaces: titanium with smooth surfaces (polished titanium (P), machined titanium (M), polyetheretherketone (Peek)), titanium with rough and hydrophilised surfaces (acid etched titanium (A), sandblasted acid etched titanium (SA and SA2), sandblasted acid etched hydrophilised (SAH), titanium plasma painted titanium (TPS)), titanium with calcium phosphate-containing surfaces (titanium plasma painted calcium phosphate modified titanium (TPS-CaP), sandblasted calcium phosphate modified titanium (S-CaP), sandblasted acid etched calcium phosphate modified titanium (SA-CaP)), and zirconium-oxide (yttrium amplified zirconium (Z), yttrium amplified Ca2+ delivering zirconium (Z-Ca))...
December 26, 2017: Journal of Cranio-maxillo-facial Surgery
Yuxia Jiao, Siqi Tan, Junyu Xiong
Sepsis is defined as life threatening organ dysfunction arising from a dysregulated host response to infection. The outcomes of sepsis include early mortality, delayed mortality and recovery, and depend on the inflammatory response. Previous studies have demonstrated that regulatory T cells (Tregs) are important in determining the outcome of sepsis, as their suppressive function serves a role in maintaining immune homeostasis. However, Treg-mediated immunosuppression during the course of sepsis remains unclear and little is known about the survival of patients following diagnosis...
December 2017: Experimental and Therapeutic Medicine
Corina Ciobanasu, Hong Wang, Véronique Henriot, Cécile Mathieu, Annabelle Fente, Sandrine Csillag, Clémence Vigouroux, Bruno Faivre, Christophe Le Clainche
Focal adhesions (FAs) mechanically couple the extracellular matrix (ECM) to the dynamic actin cytoskeleton, via transmembrane integrins and actin-binding proteins. The molecular mechanisms by which protein machineries control force transmission along this molecular axis, i.e. modulating integrin activation and controlling actin polymerization, remain largely unknown. Talin is a major actin-binding protein that controls both the inside-out activation of integrins and actin-filament anchoring and thus plays a major role in the establishment of the actin-ECM mechanical coupling...
December 24, 2017: Journal of Biological Chemistry
Liming Shen, Kaoyuan Zhang, Chengyun Feng, Youjiao Chen, Shuiming Li, Javed Iqbal, Liping Liao, Yuxi Zhao, Jian Zhai
PURPOSE: Autism is a childhood neurological disorder with poorly understood etiology and pathology. This study is designed to identify differentially expressed proteins which might serve as potential biomarkers for autism. EXPERIMENTAL DESIGN: We performed iTRAQ (isobaric tags for relative and absolute quantitation) analysis for normal and autistic children's plasma of the same age group. RESULTS: The results showed that 24 differentially expressed proteins were identified between autistic subjects and controls...
December 23, 2017: Proteomics. Clinical Applications
Jesi Y To, Alan V Smrcka
Our recent work uncovered novel roles for activated Gαi signaling in regulation of neutrophil polarity and adhesion. GαiGTP-dependent enhancement neutrophil polarization was dependent on inhibition of cAMP/PKA signaling, while reversal of Gβγ stimulated adhesion was cAMP/PKA-independent. To uncover the mechanism for Gαi regulation of adhesion, we analyzed the effects of constitutively active Gαi1(Q204L) expression on adhesion driven by constitutively active Rap1a(G12V) or its downstream effector Radil in neutrophil-like HL60 cells, or in HT-1080 fibrosarcoma cells...
December 19, 2017: Journal of Biological Chemistry
Angelia D Lockett, Yidi Wu, Susan J Gunst
Neutrophil elastase is secreted by inflammatory cells during airway inflammation and can elicit airway hyperactivity in vivo. Elastase can degrade multiple components of the extracellular matrix. We hypothesized that elastase might disrupt the connections between airway smooth muscle (ASM) cells and the extracellular matrix, and that this might have direct effects on ASM tissue responsiveness and inflammation. The effect of elastase treatment on ASM contractility was assessed in vitro in isolated strips of canine tracheal smooth muscle by stimulating tissues with cumulatively increasing concentrations of ACh and measuring contractile force...
December 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
Jakub Novák, Ivo Fabrik, Irena Linhartová, Marek Link, Ondřej Černý, Jiří Stulík, Peter Šebo
The adenylate cyclase toxin (CyaA) of the whooping cough agent Bordetella pertussis subverts immune functions of host myeloid cells expressing the αM β2 integrin (CD11b/CD18, CR3 or Mac-1). CyaA delivers into cytosol of cells an extremely catalytically active adenylyl cyclase enzyme, which disrupts the innate and adaptive immune functions of phagocytes through unregulated production of the key signaling molecule cAMP. We have used phosphoproteomics to analyze cAMP signaling of CyaA in murine bone marrow-derived dendritic cells...
November 24, 2017: Scientific Reports
Liang Zhu, Jun Yang, Thomas Bromberger, Ashley Holly, Fan Lu, Huan Liu, Kevin Sun, Sarah Klapproth, Jamila Hirbawi, Tatiana V Byzova, Edward F Plow, Markus Moser, Jun Qin
Activation of transmembrane receptor integrin by talin is essential for inducing cell adhesion. However, the pathway that recruits talin to the membrane, which critically controls talin's action, remains elusive. Membrane-anchored mammalian small GTPase Rap1 is known to bind talin-F0 domain but the binding was shown to be weak and thus hardly studied. Here we show structurally that talin-F0 binds to human Rap1b like canonical Rap1 effectors despite little sequence homology, and disruption of the binding strongly impairs integrin activation, cell adhesion, and cell spreading...
November 23, 2017: Nature Communications
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
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...
December 2017: Nature Materials
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
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
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; crucial integrins in the kidney collecting system express the β1 subunit. 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 to link them to the actin cytoskeleton...
November 15, 2017: Development
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
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
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