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Integrin talin

R E Gough, B T Goult
Talins are cytoplasmic adapter proteins essential for integrin-mediated cell adhesion to the extracellular matrix. Talins control the activation state of integrins, link integrins to cytoskeletal actin, recruit numerous signalling molecules that mediate integrin signalling, and coordinate recruitment of microtubules to adhesion sites via interaction with KANK (kidney ankyrin repeat-containing) proteins. Vertebrates have two talin genes, TLN1 and TLN2. Although talin1 and talin2 share 76% protein sequence identity (88% similarity), they are not functionally redundant, and the differences between the two isoforms are not fully understood...
May 3, 2018: FEBS Letters
Jane E Klann, Stephanie H Kim, Kelly A Remedios, Zhaoren He, Patrick J Metz, Justine Lopez, Tiffani Tysl, Jocelyn G Olvera, Jailal N Ablack, Joseph M Cantor, Brigid S Boland, Gene Yeo, Ye Zheng, Li-Fan Lu, Jack D Bui, Mark H Ginsberg, Brian G Petrich, John T Chang
Maintenance of the regulatory T (Treg) cell pool is essential for peripheral tolerance and prevention of autoimmunity. Integrins, heterodimeric transmembrane proteins consisting of α and β subunits that mediate cell-to-cell and cell-to-extracellular matrix interactions, play an important role in facilitating Treg cell contact-mediated suppression. In this article, we show that integrin activation plays an essential, previously unappreciated role in maintaining murine Treg cell function. Treg cell-specific loss of talin, a β integrin-binding protein, or expression of talin(L325R), a mutant that selectively abrogates integrin activation, resulted in lethal systemic autoimmunity...
April 27, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Rixing Zhan, Fan Wang, Ying Wu, Ying Wang, Wei Qian, Menglong Liu, Tengfei Liu, Weifeng He, Hui Ren, Gaoxing Luo
OBJECTIVE: Nitric oxide (NO) has emerged as a critical molecule in wound healing, but the mechanism underlying its activity is not well defined. Here, we explored the effect of NO on the de-adhesion of epidermal stem cells (ESCs) and the mechanism involved in this process. METHODS: The effects of NO on isolated human and mouse ESCs cultured in the presence of different concentrations of the NO donor S-nitroso-N-acetyl penicillamine (SNAP) were evaluated in cell de-adhesion assays mediated by integrin β and collagen IV...
April 23, 2018: Nitric Oxide: Biology and Chemistry
Tadayuki Yago, Nan Zhang, Liang Zhao, Charles S Abrams, Rodger P McEver
Rolling neutrophils receive signals while engaging P- and E-selectin and chemokines on inflamed endothelium. Selectin signaling activates β2 integrins to slow rolling velocities. Chemokine signaling activates β2 integrins to cause arrest. Despite extensive study, key aspects of these signaling cascades remain unresolved. Using complementary in vitro and in vivo assays, we found that selectin and chemokine signals in neutrophils triggered Rap1a-dependent and phosphatidylinositol-4-phosphate 5-kinase γ (PIP5Kγ90)-dependent pathways that induce integrin-dependent slow rolling and arrest...
April 10, 2018: Blood Advances
Terhi Savinko, Carla Guenther, Liisa M Uotila, Marc Llort Asens, Sean Yao, Sari Tojkander, Susanna C Fagerholm
T cells traffic from the bloodstream into tissues to perform their functions in the immune system and are therefore subjected to a range of different mechanical forces. Integrins are essential for T cell trafficking into the tissues, as they mediate firm adhesion between the T cell and the endothelium under shear flow conditions. In addition, integrins are important for the formation of the contact between the T cell and the APC required for T cell activation. The actin-binding protein filamin A (FlnA) provides an important link between the integrin and the actin cytoskeleton...
March 26, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Aye Myat Myat Thinn, Zhengli Wang, Jieqing Zhu
Functioning as signal receivers and transmitters, the integrin α/β cytoplasmic tails (CT) are pivotal in integrin activation and signaling. 18 α integrin subunits share a conserved membrane-proximal region but have a highly diverse membrane-distal (MD) region at their CTs. Recent studies demonstrated that the presence of α CTMD region is essential for talin-induced integrin inside-out activation. However, it remains unknown whether the non-conserved α CTMD regions differently regulate the inside-out activation of integrin...
March 22, 2018: Scientific Reports
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 22, 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...
February 6, 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))...
March 2018: 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 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-extracellular matrix mechanical coupling...
February 16, 2018: 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 that might serve as potential biomarkers for autism. EXPERIMENTAL DESIGN: We perform iTRAQ (isobaric tags for relative and absolute quantitation) analysis for normal and autistic children's plasma of the same age group. RESULTS: The results show 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 the regulation of neutrophil polarity and adhesion. Gαi GTP-mediated enhancement of neutrophil polarization was dependent on inhibition of cAMP/PKA signaling, whereas 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 HL-60 cells, or in HT-1080 fibrosarcoma cells...
February 2, 2018: 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 hyperreactivity 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 stimulation of tissues with cumulatively increasing concentrations of acetylcholine (ACh) and measurement of contractile force...
April 1, 2018: 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...
January 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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