talin

Summary

Summary: A 235-kDa cytoplasmic protein that is also found in platelets. It has been localized to regions of cell-substrate adhesion. It binds to INTEGRINS; VINCULIN; and ACTINS and appears to participate in generating a transmembrane connection between the extracellular matrix and the cytoskeleton.

Top Publications

  1. Gingras A, Vogel K, Steinhoff H, Ziegler W, Patel B, Emsley J, et al. Structural and dynamic characterization of a vinculin binding site in the talin rod. Biochemistry. 2006;45:1805-17 pubmed
    b>Talin is a key protein involved in linking integrins to the actin cytoskeleton...
  2. Zheng H, Chu J, Zeng Y, Loh H, Law P. Yin Yang 1 phosphorylation contributes to the differential effects of mu-opioid receptor agonists on microRNA-190 expression. J Biol Chem. 2010;285:21994-2002 pubmed publisher
    ..This study therefore delineates a signaling pathway that mediates the effects of fentanyl on miR-190 expression. ..
  3. Kanamori H, Kawakami T, Effendi K, Yamazaki K, Mori T, Ebinuma H, et al. Identification by differential tissue proteome analysis of talin-1 as a novel molecular marker of progression of hepatocellular carcinoma. Oncology. 2011;80:406-15 pubmed publisher
    ..tandem mass spectrometry data from those peptide peaks identified 61 proteins, including a cytoskeletal protein, talin-1, as upregulated in HCC...
  4. 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
    ..Here, we show that proteolysis of talin by the intracellular calcium-dependent protease calpain is critical for focal adhesion disassembly...
  5. Critchley D. Cytoskeletal proteins talin and vinculin in integrin-mediated adhesion. Biochem Soc Trans. 2004;32:831-6 pubmed
    The cytoskeletal proteins talin and vinculin form part of a macromolecular complex on the cytoplasmic face of integrin-mediated cellular junctions with the extracellular matrix...
  6. Anthis N, Wegener K, Critchley D, Campbell I. Structural diversity in integrin/talin interactions. Structure. 2010;18:1654-66 pubmed publisher
    The adhesion of integrins to the extracellular matrix is regulated by binding of the cytoskeletal protein talin to the cytoplasmic tail of the β-integrin subunit...
  7. 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
    b>Talin is a large dimeric protein that couples integrins to cytoskeletal actin...
  8. Petrich B, Fogelstrand P, Partridge A, Yousefi N, Ablooglu A, Shattil S, et al. The antithrombotic potential of selective blockade of talin-dependent integrin alpha IIb beta 3 (platelet GPIIb-IIIa) activation. J Clin Invest. 2007;117:2250-9 pubmed
    In vitro studies indicate that binding of talin to the beta(3) integrin cytoplasmic domain (tail) results in integrin alpha(IIb)beta(3) (GPIIb-IIIa) activation...
  9. Tanentzapf G, Brown N. An interaction between integrin and the talin FERM domain mediates integrin activation but not linkage to the cytoskeleton. Nat Cell Biol. 2006;8:601-6 pubmed
    ..b>Talin, one such linker protein, is thought to have two roles: mediating inside-out activation of integrins, and ..

Scientific Experts

More Information

Publications62

  1. Harburger D, Calderwood D. Integrin signalling at a glance. J Cell Sci. 2009;122:159-63 pubmed publisher
  2. Goult B, Zacharchenko T, Bate N, Tsang R, Hey F, Gingras A, et al. RIAM and vinculin binding to talin are mutually exclusive and regulate adhesion assembly and turnover. J Biol Chem. 2013;288:8238-49 pubmed publisher
    b>Talin activates integrins, couples them to F-actin, and recruits vinculin to focal adhesions (FAs)...
  3. 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...
  4. Himmel M, Ritter A, Rothemund S, Pauling B, Rottner K, Gingras A, et al. Control of high affinity interactions in the talin C terminus: how talin domains coordinate protein dynamics in cell adhesions. J Biol Chem. 2009;284:13832-42 pubmed publisher
    In cell-extracellular matrix junctions (focal adhesions), the cytoskeletal protein talin is central to the connection of integrins to the actin cytoskeleton...
  5. Sansing H, Sarkeshik A, Yates J, Patel V, Gutkind J, Yamada K, et al. Integrin αβ1, αvβ, α6β effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance. Biochem Biophys Res Commun. 2011;406:171-6 pubmed publisher
    ..Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel...
  6. Tuxworth R, Stephens S, Ryan Z, Titus M. Identification of a myosin VII-talin complex. J Biol Chem. 2005;280:26557-64 pubmed
  7. Dumbauld D, Shin H, Gallant N, Michael K, Radhakrishna H, Garcia A. Contractility modulates cell adhesion strengthening through focal adhesion kinase and assembly of vinculin-containing focal adhesions. J Cell Physiol. 2010;223:746-56 pubmed publisher
    ..Reductions in adhesion strengthening by inhibitors of contractility correlated with loss of vinculin and talin from focal adhesions without changes in integrin binding...
  8. 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 ..
  9. Tsujioka M, Yoshida K, Nagasaki A, Yonemura S, Müller Taubenberger A, Uyeda T. Overlapping functions of the two talin homologues in Dictyostelium. Eukaryot Cell. 2008;7:906-16 pubmed publisher
    b>Talin is a cytoskeletal protein involved in constructing and regulating focal adhesions in animal cells...
  10. Lee S, Chunsrivirot S, Kamm R, Mofrad M. Molecular dynamics study of talin-vinculin binding. Biophys J. 2008;95:2027-36 pubmed publisher
    ..Crystal structures of the unbound proteins and bound complex between the vinculin head subdomain (Vh1) and the talin vinculin binding site 1 (VBS1) indicate that vinculin undergoes a conformational change upon binding to talin...
  11. Renno W, Saleh F, Klepacek I, Al Awadi F. Talin immunogold density increases in sciatic nerve of diabetic rats after nerve growth factor treatment. Medicina (Kaunas). 2006;42:147-63 pubmed
    ..Recent studies have shown significant reduction in the activity of nerve growth factor (NGF) and in the amount of talin cytoskeleton protein immunoreactivity in the perineurium in patients with diabetic neuropathy...
  12. Goult B, Xu X, Gingras A, Swift M, Patel B, Bate N, et al. Structural studies on full-length talin1 reveal a compact auto-inhibited dimer: implications for talin activation. J Struct Biol. 2013;184:21-32 pubmed publisher
    b>Talin is a large adaptor protein that activates integrins and couples them to cytoskeletal actin. Talin contains an N-terminal FERM (band 4...
  13. Lee S, Voronov S, Letinic K, Nairn A, Di Paolo G, De Camilli P. Regulation of the interaction between PIPKI gamma and talin by proline-directed protein kinases. J Cell Biol. 2005;168:789-99 pubmed
    The interaction of talin with phosphatidylinositol(4) phosphate 5 kinase type I gamma (PIPKI gamma) regulates PI(4,5)P2 synthesis at synapses and at focal adhesions...
  14. García Bernal D, Parmo Cabañas M, Dios Esponera A, Samaniego R, Hernán P de la Ossa D, Teixido J. Chemokine-induced Zap70 kinase-mediated dissociation of the Vav1-talin complex activates alpha4beta1 integrin for T cell adhesion. Immunity. 2009;31:953-64 pubmed publisher
    ..Here we show that a Vav1-talin complex in T cells is a key target for chemokine-triggered inside-out signaling leading to integrin alpha4beta1 ..
  15. Ellis S, Goult B, Fairchild M, Harris N, Long J, Lobo P, et al. Talin autoinhibition is required for morphogenesis. Curr Biol. 2013;23:1825-33 pubmed publisher
    ..b>Talin, a FERM-domain containing protein, forms a direct link between integrin adhesion receptors and the actin ..
  16. 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 publisher
  17. Anastasi G, Cutroneo G, Gaeta R, Di Mauro D, Arco A, Consolo A, et al. Dystrophin-glycoprotein complex and vinculin-talin-integrin system in human adult cardiac muscle. Int J Mol Med. 2009;23:149-59 pubmed
    ..and they appear to comprise two protein complexes, the dystrophin-glycoprotein complex (DGC) and the vinculin-talin-integrin system...
  18. Wang P, Ballestrem C, Streuli C. The C terminus of talin links integrins to cell cycle progression. J Cell Biol. 2011;195:499-513 pubmed publisher
    ..In this paper, we examine the role of talin, an adapter protein at cell-matrix attachment sites, in outside-in signaling...
  19. Margadant F, Chew L, Hu X, Yu H, Bate N, Zhang X, et al. Mechanotransduction in vivo by repeated talin stretch-relaxation events depends upon vinculin. PLoS Biol. 2011;9:e1001223 pubmed publisher
    ..We now report that the adhesion protein, talin, is repeatedly stretched by 100-350 nm in vivo by myosin contraction of actin filaments...
  20. 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
  21. Bouaouina M, Goult B, Huet Calderwood C, Bate N, Brahme N, Barsukov I, et al. A conserved lipid-binding loop in the kindlin FERM F1 domain is required for kindlin-mediated ?IIb?3 integrin coactivation. J Biol Chem. 2012;287:6979-90 pubmed publisher
    ..Binding of the talin FERM (four-point-one, ezrin, radixin, moesin) domain to the integrin ? tail provides one key activation signal, ..
  22. Hytönen V, Vogel V. How force might activate talin's vinculin binding sites: SMD reveals a structural mechanism. PLoS Comput Biol. 2008;4:e24 pubmed publisher
    Upon cell adhesion, talin physically couples the cytoskeleton via integrins to the extracellular matrix, and subsequent vinculin recruitment is enhanced by locally applied tensile force...
  23. 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
    The talin rod contains approximately 11 vinculin binding sites (VBSs), each defined by hydrophobic residues in a series of amphipathic helices that are normally buried within the helical bundles that make up the rod...
  24. 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
    The cytoskeletal protein talin plays a key role in activating integrins and in coupling them to the actin cytoskeleton...
  25. Franco S, Perrin B, Huttenlocher A. Isoform specific function of calpain 2 in regulating membrane protrusion. Exp Cell Res. 2004;299:179-87 pubmed
    ..1, is required for proteolysis of the cytoskeletal and focal adhesion proteins FAK, paxillin, spectrin, and talin. Together, our findings support a novel role for calpain 2 in limiting membrane protrusions and in regulating ..
  26. Das M, Ithychanda S, Qin J, Plow E. Mechanisms of talin-dependent integrin signaling and crosstalk. Biochim Biophys Acta. 2014;1838:579-88 pubmed publisher
    ..or intracellular signals emanating from different signaling cascades cause inside-out signaling of integrins via talin, a cystokeletal protein that links integrins to the actin cytoskeleton...
  27. Moore D, Nygren P, Jo H, Boesze Battaglia K, Bennett J, Degrado W. Affinity of talin-1 for the ?3-integrin cytosolic domain is modulated by its phospholipid bilayer environment. Proc Natl Acad Sci U S A. 2012;109:793-8 pubmed publisher
    Binding of the talin-1 FERM (4.1/ezrin/radixin/moesin) domain to the ?3 cytosolic tail causes activation of the integrin ?IIb?3. The FERM domain also binds to acidic phospholipids...
  28. Wang Y, Litvinov R, Chen X, Bach T, Lian L, Petrich B, et al. Loss of PIP5KIgamma, unlike other PIP5KI isoforms, impairs the integrity of the membrane cytoskeleton in murine megakaryocytes. J Clin Invest. 2008;118:812-9 pubmed publisher
    ..back wild-type PIP5KIgamma, but not by adding a catalytically inactive mutant or a splice variant lacking the talin-binding motif. Notably, both PIP5KIbeta- and PIP5KIgamma(-/-) cells had impaired PIP(2) synthesis...
  29. Levi B, Ghabrial A, Krasnow M. Drosophila talin and integrin genes are required for maintenance of tracheal terminal branches and luminal organization. Development. 2006;133:2383-93 pubmed
    ..Mapping and molecular studies demonstrate that tendrils is allelic to rhea, which encodes Drosophila talin, a large cytoskeletal protein that links integrins to the cytoskeleton...
  30. Ham H, Guerrier S, Kim J, Schoon R, Anderson E, Hamann M, et al. Dedicator of cytokinesis 8 interacts with talin and Wiskott-Aldrich syndrome protein to regulate NK cell cytotoxicity. J Immunol. 2013;190:3661-9 pubmed publisher
    ..with the Wiskott-Aldrich syndrome protein, an actin nucleation-promoting factor activated by CDC42, as well as talin, which is required for integrin-mediated adhesion...
  31. Ratnikov B, Partridge A, Ginsberg M. Integrin activation by talin. J Thromb Haemost. 2005;3:1783-90 pubmed
    ..have begun to define the mechanism of integrin activation by demonstrating that binding of a cytoskeletal protein, talin, to integrin beta subunit cytoplasmic tail is a last common step in integrin activation...
  32. Smith A, Carrasco Y, Stanley P, Kieffer N, Batista F, Hogg N. A talin-dependent LFA-1 focal zone is formed by rapidly migrating T lymphocytes. J Cell Biol. 2005;170:141-51 pubmed
    ..b>Talin is essential for the stability and formation of the LFA-1 zone...
  33. Golji J, Lam J, Mofrad M. Vinculin activation is necessary for complete talin binding. Biophys J. 2011;100:332-40 pubmed publisher
    ..The growth and strengthening of these focal adhesions is dependent on the interaction between talin and vinculin. This study investigates said interaction and how vinculin activation influences it...
  34. 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
    The interaction between the cytoskeletal proteins talin and vinculin plays a key role in integrin-mediated cell adhesion and migration. We have determined the crystal structures of two domains from the talin rod spanning residues 482-789...
  35. Izard T, Evans G, Borgon R, Rush C, Bricogne G, Bois P. Vinculin activation by talin through helical bundle conversion. Nature. 2004;427:171-5 pubmed
    ..a conserved component and an essential regulator of both cell-cell (cadherin-mediated) and cell-matrix (integrin-talin-mediated focal adhesions) junctions, and it anchors these adhesion complexes to the actin cytoskeleton by binding ..
  36. Haling J, Monkley S, Critchley D, Petrich B. Talin-dependent integrin activation is required for fibrin clot retraction by platelets. Blood. 2011;117:1719-22 pubmed publisher
    b>Talin functions both as a regulator of integrin affinity and as an important mechanical link between integrins and the cytoskeleton...
  37. Izard T, Vonrhein C. Structural basis for amplifying vinculin activation by talin. J Biol Chem. 2004;279:27667-78 pubmed
    b>Talin interactions with vinculin are essential for focal adhesions. Curiously, talin contains three noncontiguous vinculin binding sites (VBS) that can bind individually to the vinculin head (Vh) domain...
  38. Anthis N, Haling J, Oxley C, Memo M, Wegener K, Lim C, et al. Beta integrin tyrosine phosphorylation is a conserved mechanism for regulating talin-induced integrin activation. J Biol Chem. 2009;284:36700-10 pubmed publisher
    ..Integrin adhesiveness for the extracellular matrix is activated by the cytoskeletal protein talin via direct binding of its phosphotyrosine-binding-like F3 domain to the cytoplasmic tail of the beta integrin ..
  39. 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...
  40. Lee H, Lim C, Puzon McLaughlin W, Shattil S, Ginsberg M. RIAM activates integrins by linking talin to ras GTPase membrane-targeting sequences. J Biol Chem. 2009;284:5119-27 pubmed publisher
    ..adaptor molecule (RIAM), a member of the MRL (Mig-10/RIAM/Lamellipodin) protein family, to promote talin-dependent integrin activation...
  41. Kiema T, Lad Y, Jiang P, Oxley C, Baldassarre M, Wegener K, et al. The molecular basis of filamin binding to integrins and competition with talin. Mol Cell. 2006;21:337-47 pubmed
    ..Notably, the structurally defined filamin binding site overlaps with that of the integrin-regulator talin, and these proteins compete for binding to integrin tails, allowing integrin-filamin interactions to impact talin-..
  42. Lin Y, Cheng Y, Huang J, Lin H, Yang B. Zap70 controls the interaction of talin with integrin to regulate the chemotactic directionality of T-cell migration. Mol Immunol. 2010;47:2022-9 pubmed publisher
    ..Instead of direct interacting with F-actin, Zap70 formed a complex with talin which is an integrin scaffold for F-actin...
  43. Calderwood D, Campbell I, Critchley D. Talins and kindlins: partners in integrin-mediated adhesion. Nat Rev Mol Cell Biol. 2013;14:503-17 pubmed publisher
    ..New data reveal the domain structure of full-length talin, provide insights into talin-mediated integrin activation and show that RIAM recruits talin to the plasma membrane,..
  44. Bois P, Borgon R, Vonrhein C, Izard T. Structural dynamics of alpha-actinin-vinculin interactions. Mol Cell Biol. 2005;25:6112-22 pubmed
    ..association with vinculin's tail domain and which differ from the alterations in Vh1 provoked by the binding of talin. Surprisingly, alphaVBS binds to Vh1 in an inverted orientation compared to the binding of talin's VBSs to ..
  45. Simonson W, Franco S, Huttenlocher A. Talin1 regulates TCR-mediated LFA-1 function. J Immunol. 2006;177:7707-14 pubmed
    ..Together, our findings indicate that TCR-induced up-regulation of LFA-1-dependent adhesiveness and resulting T cell-APC conjugation require talin1. ..
  46. Sun N, Critchley D, Paulin D, Li Z, Robson R. Identification of a repeated domain within mammalian alpha-synemin that interacts directly with talin. Exp Cell Res. 2008;314:1839-49 pubmed publisher
    ..Costameres are multi-protein assemblies enriched in the cytoskeletal proteins vinculin, alpha-actinin, and talin. We report herein a direct interaction of human alpha-synemin with the cytoskeletal protein talin by protein-..
  47. Ma Y, Qin J, Wu C, Plow E. Kindlin-2 (Mig-2): a co-activator of beta3 integrins. J Cell Biol. 2008;181:439-46 pubmed publisher
    ..It is widely accepted that the head domain of talin (talin-H) can mediate integrin activation by binding to two sites in integrin beta's CT; in integrin beta(3) this ..
  48. 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
    b>Talin is a large cytoskeletal protein that is involved in coupling the integrin family of cell adhesion molecules to the actin cytoskeleton, colocalising with the integrins in focal adhesions (FAs)...
  49. Huang C, Rajfur Z, Yousefi N, Chen Z, Jacobson K, Ginsberg M. Talin phosphorylation by Cdk5 regulates Smurf1-mediated talin head ubiquitylation and cell migration. Nat Cell Biol. 2009;11:624-30 pubmed publisher
    ..b>Talin, an actin and beta-integrin tail-binding protein, is essential for integrin activation and focal adhesion ..
  50. Jevnikar Z, Rojnik M, Jamnik P, Doljak B, Fonović U, Kos J. Cathepsin H mediates the processing of talin and regulates migration of prostate cancer cells. J Biol Chem. 2013;288:2201-9 pubmed publisher
    The cytoskeletal protein talin, an actin- and ?-integrin tail-binding protein, plays an important role in cell migration by promoting integrin activation and focal adhesion formation...
  51. Campbell I. Studies of focal adhesion assembly. Biochem Soc Trans. 2008;36:263-6 pubmed publisher
    ..These include fibronectin, integrins, talin, Dok1 and filamin...
  52. Tsujioka M, Yoshida K, Inouye K. Talin B is required for force transmission in morphogenesis of Dictyostelium. EMBO J. 2004;23:2216-25 pubmed
    b>Talin plays a key role in the assembly and stabilisation of focal adhesions, but whether it is directly involved in force transmission during morphogenesis remains to be elucidated...
  53. Franco Cea A, Ellis S, Fairchild M, Yuan L, Cheung T, Tanentzapf G. Distinct developmental roles for direct and indirect talin-mediated linkage to actin. Dev Biol. 2010;345:64-77 pubmed publisher
    ..b>Talin, one such linker protein, is essential to connect extracellular matrix-bound integrins to the cytoskeleton...