Genomes and Genes
Gene Symbol: Tln1
Description: talin 1
Alias: Tln, talin-1
- Fillingham I, Gingras A, Papagrigoriou E, Patel B, Emsley J, Critchley D, et al. A vinculin binding domain from the talin rod unfolds to form a complex with the vinculin head. Structure. 2005;13:65-74 pubmed..Interestingly, the talin 755-889 fragment binds more than one vinculin head molecule, suggesting that the talin rod may contain additional as yet unrecognized VBSs. ..
- Wegener K, Partridge A, Han J, Pickford A, Liddington R, Ginsberg M, et al. Structural basis of integrin activation by talin. Cell. 2007;128:171-82 pubmed
- Ling K, Doughman R, Firestone A, Bunce M, Anderson R. Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions. Nature. 2002;420:89-93 pubmed..This defines a mechanism for spatial generation of PtdIns(4,5)P(2) at focal adhesions. ..
- Monkley S, Zhou X, Kinston S, Giblett S, Hemmings L, Priddle H, et al. Disruption of the talin gene arrests mouse development at the gastrulation stage. Dev Dyn. 2000;219:560-74 pubmed..Therefore, the fundamental deficit in these embryos seems to be a failure of cell migration at gastrulation. ..
- Wegener K, Basran J, Bagshaw C, Campbell I, Roberts G, Critchley D, et al. Structural basis for the interaction between the cytoplasmic domain of the hyaluronate receptor layilin and the talin F3 subdomain. J Mol Biol. 2008;382:112-26 pubmed publisher..Such mutations will help to assess the importance of the interactions between talin and its various ligands in cell adhesion and migration. ..
- Petrich B, Marchese P, Ruggeri Z, Spiess S, Weichert R, Ye F, et al. Talin is required for integrin-mediated platelet function in hemostasis and thrombosis. J Exp Med. 2007;204:3103-11 pubmed..These data establish that platelet talin plays a crucial role in hemostasis and provide the first proof that talin is required for the activation and function of mammalian alpha2beta1 and alphaIIbbeta3 integrins in vivo. ..
- Barsukov I, Prescot A, Bate N, Patel B, Floyd D, Bhanji N, et al. Phosphatidylinositol phosphate kinase type 1gamma and beta1-integrin cytoplasmic domain bind to the same region in the talin FERM domain. J Biol Chem. 2003;278:31202-9 pubmed..The results suggest that ternary complex formation with a single talin FERM domain is unlikely, although both integrins and PIP kinase may bind simultaneously to the talin anti-parallel dimer. ..
- Calderwood D, Tai V, Di Paolo G, De Camilli P, Ginsberg M. Competition for talin results in trans-dominant inhibition of integrin activation. J Biol Chem. 2004;279:28889-95 pubmed..Thus, the sequestration of talin by the suppressive species is both necessary and sufficient for trans-dominant inhibition of integrin activation. ..
- Franco S, Rodgers M, Perrin B, Han J, Bennin D, Critchley D, et al. Calpain-mediated proteolysis of talin regulates adhesion dynamics. Nat Cell Biol. 2004;6:977-83 pubmed..Together, these findings identify calpain-mediated proteolysis of talin as a mechanism by which adhesion dynamics are regulated. ..
- Liang X, Sun Y, Ye M, Scimia M, Cheng H, Martin J, et al. Targeted ablation of PINCH1 and PINCH2 from murine myocardium results in dilated cardiomyopathy and early postnatal lethality. Circulation. 2009;120:568-76 pubmed publisher..These results demonstrate essential roles for PINCHs in myocardial growth, maturation, remodeling, and function and highlight the importance of studying the role of PINCHs in human cardiac injury and cardiomyopathy. ..
- Jiang G, Giannone G, Critchley D, Fukumoto E, Sheetz M. Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin. Nature. 2003;424:334-7 pubmed
- Patel B, Gingras A, Bobkov A, Fujimoto L, Zhang M, Liddington R, et al. The activity of the vinculin binding sites in talin is influenced by the stability of the helical bundles that make up the talin rod. J Biol Chem. 2006;281:7458-67 pubmed..We conclude that the stability of the helical bundles that make up the talin rod is an important factor determining the activity of the individual VBSs. ..
- Papagrigoriou E, Gingras A, Barsukov I, Bate N, Fillingham I, Patel B, et al. Activation of a vinculin-binding site in the talin rod involves rearrangement of a five-helix bundle. EMBO J. 2004;23:2942-51 pubmed..Activation of the VBS in talin and the recruitment of vinculin may support the maturation of small integrin/talin complexes into more stable adhesions. ..
- de Pereda J, Wegener K, Santelli E, Bate N, Ginsberg M, Critchley D, et al. Structural basis for phosphatidylinositol phosphate kinase type Igamma binding to talin at focal adhesions. J Biol Chem. 2005;280:8381-6 pubmed..Our data are consistent with the proposal that Src activity promotes a switch from integrin binding to PIPKIgamma binding that regulates focal adhesion turnover. ..
- Monkley S, Kostourou V, Spence L, Petrich B, Coleman S, Ginsberg M, et al. Endothelial cell talin1 is essential for embryonic angiogenesis. Dev Biol. 2011;349:494-502 pubmed publisherUsing Tln1(fl/fl);CreER mice, we show that tamoxifen-induced inactivation of the talin1 gene throughout the embryo produces an angiogenesis phenotype that is restricted to newly forming blood vessels...
- Watanabe N, Bodin L, Pandey M, Krause M, Coughlin S, Boussiotis V, et al. Mechanisms and consequences of agonist-induced talin recruitment to platelet integrin alphaIIbbeta3. J Cell Biol. 2008;181:1211-22 pubmed publisher..Thus, talin recruitment to alphaIIbbeta3 by RIAM mediates agonist-induced alphaIIbbeta3 activation, with implications for hemostasis and thrombosis. ..
- Goksoy E, Ma Y, Wang X, Kong X, Perera D, Plow E, et al. Structural basis for the autoinhibition of talin in regulating integrin activation. Mol Cell. 2008;31:124-33 pubmed publisher..These data define a distinct autoinhibition mechanism for talin and suggest how it controls integrin activation and cell adhesion. ..
- Goult B, Bate N, Anthis N, Wegener K, Gingras A, Patel B, et al. The structure of an interdomain complex that regulates talin activity. J Biol Chem. 2009;284:15097-106 pubmed publisher..The rod domain competes with beta3-integrin tails for binding to F3, and the structure of the complex suggests that the rod is also likely to sterically inhibit binding of the FERM domain to the membrane. ..
- Zhang X, Jiang G, Cai Y, Monkley S, Critchley D, Sheetz M. Talin depletion reveals independence of initial cell spreading from integrin activation and traction. Nat Cell Biol. 2008;10:1062-8 pubmed publisher..We suggest that talin is not required for initial cell spreading. However, talin provides the important mechanical linkage between ligand-bound integrins and the actin cytoskeleton required to catalyse focal adhesion-dependent pathways. ..
- Conti F, Felder A, Monkley S, Schwander M, Wood M, Lieber R, et al. Progressive myopathy and defects in the maintenance of myotendinous junctions in mice that lack talin 1 in skeletal muscle. Development. 2008;135:2043-53 pubmed publisher..Previous studies have shown that talin 1 controls the force-dependent assembly of integrin adhesion complexes and regulates the affinity of integrins for ..
- Gingras A, Bate N, Goult B, Hazelwood L, Canestrelli I, Grossmann J, et al. The structure of the C-terminal actin-binding domain of talin. EMBO J. 2008;27:458-69 pubmed..Electron microscopy provides direct evidence for binding of the dimer to F-actin and indicates that it binds to three monomers along the long-pitch helix of the actin filament. ..
- Moser M, Nieswandt B, Ussar S, Pozgajova M, Fassler R. Kindlin-3 is essential for integrin activation and platelet aggregation. Nat Med. 2008;14:325-30 pubmed publisher..We have therefore identified Kindlin-3 as a novel and essential element for platelet integrin activation in hemostasis and thrombosis. ..
- Anthis N, Wegener K, Critchley D, Campbell I. Structural diversity in integrin/talin interactions. Structure. 2010;18:1654-66 pubmed publisher..Together, these studies illustrate how the integrin/talin interaction has been fine-tuned to meet varying biological requirements. ..
- Nieswandt B, Moser M, Pleines I, Varga Szabo D, Monkley S, Critchley D, et al. Loss of talin1 in platelets abrogates integrin activation, platelet aggregation, and thrombus formation in vitro and in vivo. J Exp Med. 2007;204:3113-8 pubmed..Collectively, these experiments demonstrate that talin is required for inside-out activation of platelet integrins in hemostasis and thrombosis. ..
- Moes M, Rodius S, Coleman S, Monkley S, Goormaghtigh E, Tremuth L, et al. The integrin binding site 2 (IBS2) in the talin rod domain is essential for linking integrin beta subunits to the cytoskeleton. J Biol Chem. 2007;282:17280-8 pubmed..Our data provide the first direct evidence that IBS2 in the talin rod is essential to link integrins to the cytoskeleton. ..
- Lämmermann T, Bader B, Monkley S, Worbs T, Wedlich Soldner R, Hirsch K, et al. Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature. 2008;453:51-5 pubmed publisher..Myosin II-dependent contraction is only required on passage through narrow gaps, where a squeezing contraction of the trailing edge propels the rigid nucleus. ..
- Conti F, Monkley S, Wood M, Critchley D, Muller U. Talin 1 and 2 are required for myoblast fusion, sarcomere assembly and the maintenance of myotendinous junctions. Development. 2009;136:3597-606 pubmed publisherb>Talin 1 and 2 connect integrins to the actin cytoskeleton and regulate the affinity of integrins for ligands...
- Gingras A, Bate N, Goult B, Patel B, Kopp P, Emsley J, et al. Central region of talin has a unique fold that binds vinculin and actin. J Biol Chem. 2010;285:29577-87 pubmed publisher..In contrast, both bundles are required for actin binding. Finally, we show that the MESDc1 protein, which is predicted to have a similar fold, is a novel actin-binding protein. ..
- Menko A, Kreidberg J, Ryan T, Van Bockstaele E, Kukuruzinska M. Loss of alpha3beta1 integrin function results in an altered differentiation program in the mouse submandibular gland. Dev Dyn. 2001;220:337-49 pubmed..We conclude that alpha3beta1 is required for normal salivary cell differentiation and that its absence affects multiple components of adhesive complexes and their associated signalling pathways. ..
- Chaen T, Konno T, Egashira M, Bai R, Nomura N, Nomura S, et al. Estrogen-dependent uterine secretion of osteopontin activates blastocyst adhesion competence. PLoS ONE. 2012;7:e48933 pubmed publisher..These findings define for the first time specific regulatory components of an estrogen-dependent pathway coordinating blastocyst adhesion competence and uterine receptivity...
- Lim J, Wiedemann A, Tzircotis G, Monkley S, Critchley D, Caron E. An essential role for talin during alpha(M)beta(2)-mediated phagocytosis. Mol Biol Cell. 2007;18:976-85 pubmed..Our results establish for the first time at least two distinct roles for talin during CR3/alpha(M)beta(2)-mediated phagocytosis, most noticeably activation of the CR3/alpha(M)beta(2) receptor and phagocytic uptake. ..
- Manso A, Li R, Monkley S, Cruz N, Ong S, Lao D, et al. Talin1 has unique expression versus talin 2 in the heart and modifies the hypertrophic response to pressure overload. J Biol Chem. 2013;288:4252-64 pubmed publisher..Talin (Tln) activates integrins and links it to the actin cytoskeleton. Vertebrates contain two talin genes, tln1 and tln2. How Tln1 and Tln2 function in cardiac myocytes (CMs) is unknown...
- Mace E, Monkley S, Critchley D, Takei F. A dual role for talin in NK cell cytotoxicity: activation of LFA-1-mediated cell adhesion and polarization of NK cells. J Immunol. 2009;182:948-56 pubmed..Thus, talin1 plays a dual role in NK cell cytotoxicity, first by activation of LFA-1-mediated adhesion and then via LFA-1-induced NK cell polarization. ..
- Kwapiszewska G, Wygrecka M, Marsh L, Schmitt S, Trösser R, Wilhelm J, et al. Fhl-1, a new key protein in pulmonary hypertension. Circulation. 2008;118:1183-94 pubmed publisher..Coimmunoprecipitation experiments identified Talin1 as a new interacting partner of Fhl-1. Protein screening identified Fhl-1 as a novel protein regulated in various forms of PH, including idiopathic pulmonary arterial hypertension. ..
- Ketelaar T, Anthony R, Hussey P. Green fluorescent protein-mTalin causes defects in actin organization and cell expansion in Arabidopsis and inhibits actin depolymerizing factor's actin depolymerizing activity in vitro. Plant Physiol. 2004;136:3990-8 pubmed..These observations demonstrate that GFP-mTalin can affect cell expansion, actin organization, and the interaction of actin binding proteins with actin. ..
- Gunawan M, Venkatesan N, Loh J, Wong J, Berger H, Neo W, et al. The methyltransferase Ezh2 controls cell adhesion and migration through direct methylation of the extranuclear regulatory protein talin. Nat Immunol. 2015;16:505-16 pubmed publisher..Our studies reveal an unforeseen extranuclear function for Ezh2 in regulating adhesion dynamics, with implications for leukocyte migration, immune responses and potentially pathogenic processes. ..
- Palmer S, Groves N, Schindeler A, Yeoh T, Biben C, Wang C, et al. The small muscle-specific protein Csl modifies cell shape and promotes myocyte fusion in an insulin-like growth factor 1-dependent manner. J Cell Biol. 2001;153:985-98 pubmed
- Nader G, Ezratty E, Gundersen G. FAK, talin and PIPKI? regulate endocytosed integrin activation to polarize focal adhesion assembly. Nat Cell Biol. 2016;18:491-503 pubmed publisher..We propose that the conformational memory of endocytosed integrin enhances polarized reassembly of FAs to enable directional cell migration. ..
- Hyduk S, Rullo J, Cano A, Xiao H, Chen M, Moser M, et al. Talin-1 and kindlin-3 regulate alpha4beta1 integrin-mediated adhesion stabilization, but not G protein-coupled receptor-induced affinity upregulation. J Immunol. 2011;187:4360-8 pubmed publisher..Talin-1 contributed to ?(4)?(1)-dependent chemotaxis, suggesting that it participates in a later stage of the leukocyte adhesion cascade when the leukocyte cytoskeleton undergoes dramatic rearrangement...
- Roca Cusachs P, Gauthier N, Del Rio A, Sheetz M. Clustering of alpha(5)beta(1) integrins determines adhesion strength whereas alpha(v)beta(3) and talin enable mechanotransduction. Proc Natl Acad Sci U S A. 2009;106:16245-50 pubmed publisher..Importantly, we did not detect a role of either integrin alpha(v)beta(3) or talin 1 or 2 in maintaining adhesion strength...
- Kong X, Wang X, Misra S, Qin J. Structural basis for the phosphorylation-regulated focal adhesion targeting of type Igamma phosphatidylinositol phosphate kinase (PIPKIgamma) by talin. J Mol Biol. 2006;359:47-54 pubmed
- Bois P, O Hara B, Nietlispach D, Kirkpatrick J, Izard T. The vinculin binding sites of talin and alpha-actinin are sufficient to activate vinculin. J Biol Chem. 2006;281:7228-36 pubmed
- Freiberg B, Kupfer H, Maslanik W, Delli J, Kappler J, Zaller D, et al. Staging and resetting T cell activation in SMACs. Nat Immunol. 2002;3:911-7 pubmed..We propose that pre-SMAC signals are sufficient to activate cell adhesion, but not productive T cell responses, which require orchestrated signaling in SMACs. ..
- Wernimont S, Wiemer A, Bennin D, Monkley S, Ludwig T, Critchley D, et al. Contact-dependent T cell activation and T cell stopping require talin1. J Immunol. 2011;187:6256-67 pubmed publisher..These results indicate that T cell proliferation requires sustained, talin1-mediated T cell-APC interactions and that talin1 is necessary for F-actin polarization and the stability of the IS. ..
- Debrand E, Conti F, Bate N, Spence L, Mazzeo D, Pritchard C, et al. Mice carrying a complete deletion of the talin2 coding sequence are viable and fertile. Biochem Biophys Res Commun. 2012;426:190-5 pubmed publisher..However, the number of Tln2(cd/cd) pups surviving to adulthood was variable suggesting that such mice have an underlying defect. ..
- OrÅ‚owski A, Kukkurainen S, PÃ¶yry A, Rissanen S, Vattulainen I, HytÃ¶nen V, et al. PIP2 and Talin Join Forces to Activate Integrin. J Phys Chem B. 2015;119:12381-9 pubmed publisher..Our results provide a new perspective on the role of PIP2 in integrin activation and indicate that the charged PIP2 lipid headgroup can perturb a clasp at the cytoplasmic face of the integrin heterodimer. ..
- Gilmore A, Ohanian V, Spurr N, Critchley D. Localisation of the human gene encoding the cytoskeletal protein talin to chromosome 9p. Hum Genet. 1995;96:221-4 pubmed..Deletions in 9p have been implicated in a variety of cancers, including malignant melanoma, and the concept that talin might be a candidate tumour suppressor gene is discussed. ..