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Gene Review

TLN1  -  talin 1

Homo sapiens

Synonyms: ILWEQ, KIAA1027, TLN, Talin-1
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Disease relevance of TLN1


High impact information on TLN1

  • Structural basis of integrin activation by talin [6].
  • We used structure-based mutagenesis to engineer talin and beta3 variants that interact with comparable affinity to the wild-type proteins but inhibit integrin activation by competing with endogenous talin [6].
  • The interface interactions are disrupted by point mutations or the cytoskeletal protein talin that are known to activate the receptor [7].
  • Here we show that the type I phosphatidylinositol phosphate kinase isoform-gamma 661 (PIPKI gamma 661), an enzyme that makes PtdIns(4,5)P(2), is targeted to focal adhesions by an association with talin [8].
  • Phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P(2)) regulates interactions between these proteins, including the interaction of vinculin with actin and talin [8].

Biological context of TLN1

  • Our results also show that FAK can be localized independent of its phosphorylation and that cells can spread and induce localization of other focal adhesion proteins in the absence of detectable talin [9].
  • Curiously, talin contains three noncontiguous vinculin binding sites (VBS) that can bind individually to the vinculin head (Vh) domain [10].
  • Here, we demonstrate for the first time the in vivo relevance of this interaction by fluorescence resonance energy transfer between beta(3)-GFP and DsRed-talin fragment G [11].
  • These results demonstrate that activation of the integrin-binding activity of talin requires not only integrin engagement to the extracellular matrix but also the binding of PI4,5P(2) to talin, suggesting a possible role of lipid metabolism in organizing the sequential assembly of focal adhesion components [12].
  • In this report, we show that in talin-deficient AT22 cells, the aberrant glycosylation of integrin receptors is accompanied by a delay in the export of the integrin alpha5beta1 [13].

Anatomical context of TLN1


Associations of TLN1 with chemical compounds


Physical interactions of TLN1

  • Vinculin is autoinhibited by an intramolecular interaction that masks binding sites for talin and F-actin [20].
  • Calpain cleavage promotes talin binding to the beta 3 integrin cytoplasmic domain [16].
  • The critical residues in the talin FERM domain that mediate integrin binding show a high degree of conservation in kindlerin [21].
  • Furthermore, we have correlated the ability of integrin to induce FAK phosphorylation with its ability to bind talin using a mutant integrin lacking the carboxyl-terminal 13 amino acids [22].
  • Here, we utilized "homology scanning" mutagenesis to identify beta tail mutants selectively defective in c-Src binding and found that amino acid exchanges affecting a combination of an Arg and Thr residue in the integrin beta3 tail control the binding specificity for SFKs but have no effect on talin binding [23].

Co-localisations of TLN1

  • Integrin alpha-chains colocalized with talin, dependent on the matrix substrate [24].
  • These two proteins share a region of homology with talin and members of the FERM superfamily of proteins.We have determined that a functional UNC-112::GFP fusion protein colocalizes with PAT-3/beta-integrin in both adult and embryonic body wall muscle [25].
  • Hence, F-actin and the cytoskeletal protein talin co-localized with beta 1 and alpha 4 integrin clusters at sites of cell-cell contact [26].

Regulatory relationships of TLN1

  • Here we report the crystal structure of the human Vh.VBS1 complex, a validated model of the Vh.VBS2 structure, and biochemical studies that demonstrate that all of talin VBSs activate vinculin by provoking helical bundle conversion of the Vh domain, which displaces the vinculin tail (Vt) domain [10].
  • Moreover, the interaction between integrin and talin was greatly enhanced by PI4,5P(2)-induced talin activation [12].
  • Talin controls the exit of the integrin alpha 5 beta 1 from an early compartment of the secretory pathway [13].
  • PDGF stimulation induces phosphorylation of talin and cytoskeletal reorganization in skeletal muscle [27].
  • ICAP-1 alpha induced a rapid disruption of focal adhesions, which may result from the ability of ICAP-1 alpha to inhibit the association of beta(1A) integrin with talin, which is crucial for the assembly of these structures [28].
  • In this study using transfectants and T cells, we showed that talin induced an intermediate affinity alphaLbeta2 that adhered constitutively to its ligand intercellular adhesion molecule (ICAM)-1 but not ICAM-3 [29].

Other interactions of TLN1

  • Yeast two-hybrid and biochemical analyses yielded interactions with several focal adhesion and/or cytoskeletal proteins including mena, zyxin and talin [30].
  • An additional duplication subsequently produced a second Talin-2 in teleost fishes and a second Talin-1 in Xenopus laevis [31].
  • We examined the progressive appearance of the following proteins: alpha, beta, gamma, delta-sarcoglycans, beta-dystroglycan, dystrophin, talin, vinculin and integrin isoform alpha(7)/beta(1) [32].
  • These data show that the talin FERM domain, like that in the ERM proteins, is masked in the intact molecule [16].
  • We propose that talin binding to the integrin may disclose a diphenylalanine export signal, which is present in the membrane-proximal GFFKR motif conserved in all integrin alpha chains [13].

Analytical, diagnostic and therapeutic context of TLN1


  1. Localisation of the human gene encoding the cytoskeletal protein talin to chromosome 9p. Gilmore, A.P., Ohanian, V., Spurr, N.K., Critchley, D.R. Hum. Genet. (1995) [Pubmed]
  2. Cytoskeletal rearrangements accompanying salmonella entry into epithelial cells. Finlay, B.B., Ruschkowski, S., Dedhar, S. J. Cell. Sci. (1991) [Pubmed]
  3. Structural mimicry for vinculin activation by IpaA, a virulence factor of Shigella flexneri. Hamiaux, C., van Eerde, A., Parsot, C., Broos, J., Dijkstra, B.W. EMBO Rep. (2006) [Pubmed]
  4. Purification and characterization of an 85 kDa talin-binding fragment of vinculin. Groesch, M.E., Otto, J.J. Cell Motil. Cytoskeleton (1990) [Pubmed]
  5. Perineurium talin immunoreactivity decreases in diabetic neuropathy. Mazzeo, A., Rodolico, C., Monici, M.C., Migliorato, A., Aguennouz, M., Vita, G. J. Neurol. Sci. (1997) [Pubmed]
  6. Structural basis of integrin activation by talin. Wegener, K.L., Partridge, A.W., Han, J., Pickford, A.R., Liddington, R.C., Ginsberg, M.H., Campbell, I.D. Cell (2007) [Pubmed]
  7. A structural mechanism of integrin alpha(IIb)beta(3) "inside-out" activation as regulated by its cytoplasmic face. Vinogradova, O., Velyvis, A., Velyviene, A., Hu, B., Haas, T., Plow, E., Qin, J. Cell (2002) [Pubmed]
  8. Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions. Ling, K., Doughman, R.L., Firestone, A.J., Bunce, M.W., Anderson, R.A. Nature (2002) [Pubmed]
  9. Protein kinase C regulates alpha v beta 5-dependent cytoskeletal associations and focal adhesion kinase phosphorylation. Lewis, J.M., Cheresh, D.A., Schwartz, M.A. J. Cell Biol. (1996) [Pubmed]
  10. Structural basis for amplifying vinculin activation by talin. Izard, T., Vonrhein, C. J. Biol. Chem. (2004) [Pubmed]
  11. A fluorescence cell biology approach to map the second integrin-binding site of talin to a 130-amino acid sequence within the rod domain. Tremuth, L., Kreis, S., Melchior, C., Hoebeke, J., Rondé, P., Plançon, S., Takeda, K., Kieffer, N. J. Biol. Chem. (2004) [Pubmed]
  12. Conformation, localization, and integrin binding of talin depend on its interaction with phosphoinositides. Martel, V., Racaud-Sultan, C., Dupe, S., Marie, C., Paulhe, F., Galmiche, A., Block, M.R., Albiges-Rizo, C. J. Biol. Chem. (2001) [Pubmed]
  13. Talin controls the exit of the integrin alpha 5 beta 1 from an early compartment of the secretory pathway. Martel, V., Vignoud, L., Dupé, S., Frachet, P., Block, M.R., Albigès-Rizo, C. J. Cell. Sci. (2000) [Pubmed]
  14. A talin-dependent LFA-1 focal zone is formed by rapidly migrating T lymphocytes. Smith, A., Carrasco, Y.R., Stanley, P., Kieffer, N., Batista, F.D., Hogg, N. J. Cell Biol. (2005) [Pubmed]
  15. Vinculin, talin, and integrins are localized at specific adhesion sites of malignant B lymphocytes. Marchisio, P.C., Bergui, L., Corbascio, G.C., Cremona, O., D'Urso, N., Schena, M., Tesio, L., Caligaris-Cappio, F. Blood (1988) [Pubmed]
  16. Calpain cleavage promotes talin binding to the beta 3 integrin cytoplasmic domain. Yan, B., Calderwood, D.A., Yaspan, B., Ginsberg, M.H. J. Biol. Chem. (2001) [Pubmed]
  17. Hsp72 interacts with paxillin and facilitates the reassembly of focal adhesions during recovery from ATP depletion. Mao, H., Wang, Y., Li, Z., Ruchalski, K.L., Yu, X., Schwartz, J.H., Borkan, S.C. J. Biol. Chem. (2004) [Pubmed]
  18. Integrin function: molecular hierarchies of cytoskeletal and signaling molecules. Miyamoto, S., Teramoto, H., Coso, O.A., Gutkind, J.S., Burbelo, P.D., Akiyama, S.K., Yamada, K.M. J. Cell Biol. (1995) [Pubmed]
  19. Talin: an emerging focal point of adhesion dynamics. Nayal, A., Webb, D.J., Horwitz, A.F. Curr. Opin. Cell Biol. (2004) [Pubmed]
  20. Two distinct head-tail interfaces cooperate to suppress activation of vinculin by talin. Cohen, D.M., Chen, H., Johnson, R.P., Choudhury, B., Craig, S.W. J. Biol. Chem. (2005) [Pubmed]
  21. The Kindler syndrome protein is regulated by transforming growth factor-beta and involved in integrin-mediated adhesion. Kloeker, S., Major, M.B., Calderwood, D.A., Ginsberg, M.H., Jones, D.A., Beckerle, M.C. J. Biol. Chem. (2004) [Pubmed]
  22. Interaction of focal adhesion kinase with cytoskeletal protein talin. Chen, H.C., Appeddu, P.A., Parsons, J.T., Hildebrand, J.D., Schaller, M.D., Guan, J.L. J. Biol. Chem. (1995) [Pubmed]
  23. Specification of the direction of adhesive signaling by the integrin beta cytoplasmic domain. Arias-Salgado, E.G., Lizano, S., Shattil, S.J., Ginsberg, M.H. J. Biol. Chem. (2005) [Pubmed]
  24. Alpha 3 beta 1 integrin is moved into focal contacts in kidney mesangial cells. Grenz, H., Carbonetto, S., Goodman, S.L. J. Cell. Sci. (1993) [Pubmed]
  25. The UNC-112 gene in Caenorhabditis elegans encodes a novel component of cell-matrix adhesion structures required for integrin localization in the muscle cell membrane. Rogalski, T.M., Mullen, G.P., Gilbert, M.M., Williams, B.D., Moerman, D.G. J. Cell Biol. (2000) [Pubmed]
  26. Co-clustering of beta 1 integrins, cytoskeletal proteins, and tyrosine-phosphorylated substrates during integrin-mediated leukocyte aggregation. Sánchez-Mateos, P., Campanero, M.R., Balboa, M.A., Sánchez-Madrid, F. J. Immunol. (1993) [Pubmed]
  27. PDGF stimulation induces phosphorylation of talin and cytoskeletal reorganization in skeletal muscle. Tidball, J.G., Spencer, M.J. J. Cell Biol. (1993) [Pubmed]
  28. Disruption of focal adhesions by integrin cytoplasmic domain-associated protein-1 alpha. Bouvard, D., Vignoud, L., Dupé-Manet, S., Abed, N., Fournier, H.N., Vincent-Monegat, C., Retta, S.F., Fassler, R., Block, M.R. J. Biol. Chem. (2003) [Pubmed]
  29. The cytosolic protein talin induces an intermediate affinity integrin alphaLbeta2. Li, Y.F., Tang, R.H., Puan, K.J., Law, S.K., Tan, S.M. J. Biol. Chem. (2007) [Pubmed]
  30. TES is a novel focal adhesion protein with a role in cell spreading. Coutts, A.S., MacKenzie, E., Griffith, E., Black, D.M. J. Cell. Sci. (2003) [Pubmed]
  31. Gene duplication and functional divergence during evolution of the cytoskeletal linker protein talin. Senetar, M.A., McCann, R.O. Gene (2005) [Pubmed]
  32. Culture of human skeletal muscle myoblasts: timing appearance and localization of dystrophin-glycoprotein complex and vinculin-talin-integrin complex. Trimarchi, F., Favaloro, A., Fulle, S., Magaudda, L., Puglielli, C., Di Mauro, D. Cells Tissues Organs (Print) (2006) [Pubmed]
  33. Identification of a talin-binding site in the integrin beta(3) subunit distinct from the NPLY regulatory motif of post-ligand binding functions. The talin n-terminal head domain interacts with the membrane-proximal region of the beta(3) cytoplasmic tail. Patil, S., Jedsadayanmata, A., Wencel-Drake, J.D., Wang, W., Knezevic, I., Lam, S.C. J. Biol. Chem. (1999) [Pubmed]
  34. Characterization of the human talin (TLN) gene: genomic structure, chromosomal localization, and expression pattern. Ben-Yosef, T., Francomano, C.A. Genomics (1999) [Pubmed]
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