TLN1

TLN1
Identifiers
AliasesTLN1, ILWEQ, TLN, talin 1, talin-1
External IDsOMIM: 186745; MGI: 1099832; GeneCards: TLN1
Available structures
PDBOrtholog search: PDBe RCSB
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
Entrez

7094

21894

Ensembl

ENSG00000137076

ENSMUSG00000028465

UniProt

Q9Y490

P26039

RefSeq (mRNA)

NM_006289

NM_011602

RefSeq (protein)

NP_006280

NP_035732

Location (UCSC)Chr 9: 35.7 – 35.73 MbChr 4: 43.53 – 43.56 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

Talin-1 is a protein that in humans is encoded by the TLN1 gene. Talin-1 is ubiquitously expressed, and is localized to costamere structures in cardiac and skeletal muscle cells, and to focal adhesions in smooth muscle and non-muscle cells. Talin-1 functions to mediate cell-cell adhesion via the linkage of integrins to the actin cytoskeleton and in the activation of integrins. Altered expression of talin-1 has been observed in patients with heart failure, however no mutations in TLN1 have been linked with specific diseases.

Structure

Human talin-1 is 270.0 kDa molecular weight and 2541 amino acids. The N-terminal region of talin-1 is ~50 kDa in size and homologous to members of the ERM protein family which have a globular FERM domain (residues 86-400) that links the actin cytoskeleton to adhesion proteins. In addition to F-actin, the N-terminal region of talin-1 binds layilin, β1- and β3-integrin, and focal adhesion kinase. Talin-1 N-terminal region also binds acidic phospholipids for insertion into lipid bilayers. The rod domain (>200 kDa) has considerable flexibility and houses a conserved actin binding site, three vinculin binding sites, and also has an additional integrin binding site, termed IBS2. The head and rod domains are connected by an unstructured linker region (residues 401-481), which houses several sites of phosphorylation, as well as protease cleavage. Talin-1 can homodimerize in an antiparallel fashion, however, talin-1 and its closely related counterpart, talin-2 do not form heterodimers.

Function

In mammals talin-1 is ubiquitously expressed; talin-1 is found complexed to integrins and localized to intercalated discs of cardiac muscle and to costamere structures of both skeletal and cardiac muscles, in correspondence with the I-band and M-line. Talin-1 is also found at focal adhesions of smooth muscle cells and non-muscle cells.

In undifferentiated cultures of myoblasts, talin-1 expression is perinuclear, and then progresses to a cytoplasmic distribution followed by a sarcomlemmal, costameric-like pattern by day 15 of differentiation. Homozygous disruption of TLN1 in mice is embryonic lethal, demonstrating that talin-1 is required for normal embryogenesis. It has been shown, however, that talin-1 expression is minor in adult cardiomyocytes, and becomes more prominent at costameres during cardiac hypertrophy induced by pharmacological and mechanical stress.

The primary function of talin-1 involves the linkage of integrins to the actin cytoskeleton and in the energy-dependent activation of integrins. Functions for talin-1 in specific tissues have been illuminated through conditional knockout animals. Studies employing the conditional knockout of talin 1 in skeletal muscle have demonstrated its role in maintaining integrin attachment sites at myotendinous junctions; knockout mice develop progressive myopathy and show deficits in muscle force generation. In platelets, conditional knockout of talin-1 results in the inability to activate integrins in response to platelet agonists, resulting in mice with severe hemostatic defects and resistance to arterial thrombosis. Conditional knockout of talin-1 in cardiomyocytes shows that mice have normal cardiac function at baseline, but improved function, blunted hypertrophy, and attenuated fibrosis when subjected to pressure overload-induced cardiac hypertrophy, which correlated with blunted ERK1/2, p38, Akt, and glycogen synthase kinase 3 responses. These data suggest that upregulation of talin-1 in cardiac hypertrophy may be detrimental to cardiomyocytes function.

Clinical significance

In patients with heart failure, talin-1 expression in cardiomyocytes is increased relative to control cells.

Interactions

TLN1 has been shown to interact with:

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000137076 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028465 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Gilmore AP, Ohanian V, Spurr NK, Critchley DR (Aug 1995). "Localisation of the human gene encoding the cytoskeletal protein talin to chromosome 9p". Human Genetics. 96 (2): 221–4. doi:10.1007/BF00207384. PMID 7635475. S2CID 38856479.
  6. ↑ Ben-Yosef T, Francomano CA (Dec 1999). "Characterization of the human talin (TLN) gene: genomic structure, chromosomal localization, and expression pattern". Genomics. 62 (2): 316–9. doi:10.1006/geno.1999.6019. PMID 10610730.
  7. ↑ "Protein sequence of human TLN1 (Uniprot ID: Q9Y490)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 8 July 2015. Retrieved 7 July 2015.
  8. ↑ Hamada K, Shimizu T, Matsui T, Tsukita S, Hakoshima T (Sep 2000). "Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain". The EMBO Journal. 19 (17): 4449–62. doi:10.1093/emboj/19.17.4449. PMC 302071. PMID 10970839.
  9. 1 2 3 Critchley DR (2009). "Biochemical and structural properties of the integrin-associated cytoskeletal protein talin". Annual Review of Biophysics. 38: 235–54. doi:10.1146/annurev.biophys.050708.133744. PMID 19416068.
  10. 1 2 3 Hemmings L, Rees DJ, Ohanian V, Bolton SJ, Gilmore AP, Patel B, Priddle H, Trevithick JE, Hynes RO, Critchley DR (Nov 1996). "Talin contains three actin-binding sites each of which is adjacent to a vinculin-binding site" (PDF). Journal of Cell Science. 109 (11): 2715–26. doi:10.1242/jcs.109.11.2715. PMID 8937989.
  11. 1 2 Borowsky ML, Hynes RO (Oct 1998). "Layilin, a novel talin-binding transmembrane protein homologous with C-type lectins, is localized in membrane ruffles". The Journal of Cell Biology. 143 (2): 429–42. doi:10.1083/jcb.143.2.429. PMC 2132847. PMID 9786953.
  12. 1 2 Patil S, Jedsadayanmata A, Wencel-Drake JD, Wang W, Knezevic I, Lam SC (Oct 1999). "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". The Journal of Biological Chemistry. 274 (40): 28575–83. doi:10.1074/jbc.274.40.28575. PMID 10497223.
  13. 1 2 Calderwood DA, Yan B, de Pereda JM, Alvarez BG, Fujioka Y, Liddington RC, Ginsberg MH (Jun 2002). "The phosphotyrosine binding-like domain of talin activates integrins". The Journal of Biological Chemistry. 277 (24): 21749–58. doi:10.1074/jbc.M111996200. PMID 11932255.
  14. 1 2 Calderwood DA, Zent R, Grant R, Rees DJ, Hynes RO, Ginsberg MH (Oct 1999). "The Talin head domain binds to integrin beta subunit cytoplasmic tails and regulates integrin activation". The Journal of Biological Chemistry. 274 (40): 28071–4. doi:10.1074/jbc.274.40.28071. PMID 10497155.
  15. 1 2 Chen HC, Appeddu PA, Parsons JT, Hildebrand JD, Schaller MD, Guan JL (Jul 1995). "Interaction of focal adhesion kinase with cytoskeletal protein talin". The Journal of Biological Chemistry. 270 (28): 16995–9. doi:10.1074/jbc.270.28.16995. PMID 7622520.
  16. 1 2 Zheng C, Xing Z, Bian ZC, Guo C, Akbay A, Warner L, Guan JL (Jan 1998). "Differential regulation of Pyk2 and focal adhesion kinase (FAK). The C-terminal domain of FAK confers response to cell adhesion". The Journal of Biological Chemistry. 273 (4): 2384–9. doi:10.1074/jbc.273.4.2384. PMID 9442086.
  17. ↑ Dietrich C, Goldmann WH, Sackmann E, Isenberg G (Jun 1993). "Interaction of NBD-talin with lipid monolayers. A film balance study". FEBS Letters. 324 (1): 37–40. doi:10.1016/0014-5793(93)81527-7. PMID 8504857. S2CID 20868168.
  18. ↑ Goldmann WH, Niggli V, Kaufmann S, Isenberg G (Aug 1992). "Probing actin and liposome interaction of talin and talin-vinculin complexes: a kinetic, thermodynamic and lipid labeling study". Biochemistry. 31 (33): 7665–71. doi:10.1021/bi00148a030. PMID 1510952.
  19. ↑ Heise H, Bayerl T, Isenberg G, Sackmann E (Jan 1991). "Human platelet P-235, a talin-like actin binding protein, binds selectively to mixed lipid bilayers". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1061 (2): 121–31. doi:10.1016/0005-2736(91)90276-e. PMID 1900196.
  20. 1 2 Bass MD, Smith BJ, Prigent SA, Critchley DR (Jul 1999). "Talin contains three similar vinculin-binding sites predicted to form an amphipathic helix". The Biochemical Journal. 341 (2): 257–63. doi:10.1042/bj3410257. PMC 1220354. PMID 10393080.
  21. 1 2 Gilmore AP, Wood C, Ohanian V, Jackson P, Patel B, Rees DJ, Hynes RO, Critchley DR (Jul 1993). "The cytoskeletal protein talin contains at least two distinct vinculin binding domains". The Journal of Cell Biology. 122 (2): 337–47. doi:10.1083/jcb.122.2.337. PMC 2119638. PMID 8320257.
  22. 1 2 Burridge K, Mangeat P (1984). "An interaction between vinculin and talin". Nature. 308 (5961): 744–6. Bibcode:1984Natur.308..744B. doi:10.1038/308744a0. PMID 6425696. S2CID 4316613.
  23. ↑ Horwitz A, Duggan K, Buck C, Beckerle MC, Burridge K (1986). "Interaction of plasma membrane fibronectin receptor with talin--a transmembrane linkage". Nature. 320 (6062): 531–3. Bibcode:1986Natur.320..531H. doi:10.1038/320531a0. PMID 2938015. S2CID 4356748.
  24. ↑ Moes M, Rodius S, Coleman SJ, Monkley SJ, Goormaghtigh E, Tremuth L, Kox C, van der Holst PP, Critchley DR, Kieffer N (Jun 2007). "The integrin binding site 2 (IBS2) in the talin rod domain is essential for linking integrin beta subunits to the cytoskeleton". The Journal of Biological Chemistry. 282 (23): 17280–8. doi:10.1074/jbc.M611846200. PMID 17430904.
  25. ↑ Rodius S, Chaloin O, Moes M, Schaffner-Reckinger E, Landrieu I, Lippens G, Lin M, Zhang J, Kieffer N (Aug 2008). "The talin rod IBS2 alpha-helix interacts with the beta3 integrin cytoplasmic tail membrane-proximal helix by establishing charge complementary salt bridges". The Journal of Biological Chemistry. 283 (35): 24212–23. doi:10.1074/jbc.M709704200. PMC 3259754. PMID 18577523.
  26. ↑ Tremuth L, Kreis S, Melchior C, Hoebeke J, Rondé P, Plançon S, Takeda K, Kieffer N (May 2004). "A fluorescence cell biology approach to map the second integrin-binding site of talin to a 130-amino acid sequence within the rod domain". The Journal of Biological Chemistry. 279 (21): 22258–66. doi:10.1074/jbc.M400947200. PMID 15031296.
  27. ↑ Xing B, Jedsadayanmata A, Lam SC (Nov 2001). "Localization of an integrin binding site to the C terminus of talin". The Journal of Biological Chemistry. 276 (48): 44373–8. doi:10.1074/jbc.M108587200. PMID 11555663.
  28. ↑ Ratnikov B, Ptak C, Han J, Shabanowitz J, Hunt DF, Ginsberg MH (Nov 2005). "Talin phosphorylation sites mapped by mass spectrometry". Journal of Cell Science. 118 (Pt 21): 4921–3. doi:10.1242/jcs.02682. PMID 16254238.
  29. ↑ Rees DJ, Ades SE, Singer SJ, Hynes RO (Oct 1990). "Sequence and domain structure of talin". Nature. 347 (6294): 685–9. Bibcode:1990Natur.347..685R. doi:10.1038/347685a0. PMID 2120593. S2CID 4274654.
  30. ↑ Molony L, McCaslin D, Abernethy J, Paschal B, Burridge K (Jun 1987). "Properties of talin from chicken gizzard smooth muscle". The Journal of Biological Chemistry. 262 (16): 7790–5. doi:10.1016/S0021-9258(18)47637-5. PMID 3108258.
  31. ↑ Praekelt U, Kopp PM, Rehm K, Linder S, Bate N, Patel B, Debrand E, Manso AM, Ross RS, Conti F, Zhang MZ, Harris RC, Zent R, Critchley DR, Monkley SJ (Mar 2012). "New isoform-specific monoclonal antibodies reveal different sub-cellular localisations for talin1 and talin2". European Journal of Cell Biology. 91 (3): 180–91. doi:10.1016/j.ejcb.2011.12.003. PMC 3629562. PMID 22306379.
  32. ↑ Belkin AM, Zhidkova NI, Koteliansky VE (May 1986). "Localization of talin in skeletal and cardiac muscles". FEBS Letters. 200 (1): 32–6. doi:10.1016/0014-5793(86)80505-1. PMID 3084298.
  33. ↑ Anastasi G, Cutroneo G, Gaeta R, Di Mauro D, Arco A, Consolo A, Santoro G, Trimarchi F, Favaloro A (Feb 2009). "Dystrophin-glycoprotein complex and vinculin-talin-integrin system in human adult cardiac muscle". International Journal of Molecular Medicine. 23 (2): 149–59. doi:10.3892/ijmm_00000112. PMID 19148538.
  34. ↑ Mondello MR, Bramanti P, Cutroneo G, Santoro G, Di Mauro D, Anastasi G (Jul 1996). "Immunolocalization of the costameres in human skeletal muscle fibers: confocal scanning laser microscope investigations". The Anatomical Record. 245 (3): 481–7. doi:10.1002/(SICI)1097-0185(199607)245:3<481::AID-AR4>3.0.CO;2-V. PMID 8800406.
  35. ↑ Wu JC, Sung HC, Chung TH, DePhilip RM (2002). "Role of N-cadherin- and integrin-based costameres in the development of rat cardiomyocytes". Journal of Cellular Biochemistry. 84 (4): 717–24. doi:10.1002/jcb.10092. PMID 11835397. S2CID 28938842.
  36. ↑ Burridge K, Connell L (Aug 1983). "A new protein of adhesion plaques and ruffling membranes". The Journal of Cell Biology. 97 (2): 359–67. doi:10.1083/jcb.97.2.359. PMC 2112532. PMID 6684120.
  37. ↑ Trimarchi F, Favaloro A, Fulle S, Magaudda L, Puglielli C, Di Mauro D (2006). "Culture of human skeletal muscle myoblasts: timing appearance and localization of dystrophin-glycoprotein complex and vinculin-talin-integrin complex". Cells Tissues Organs. 183 (2): 87–98. doi:10.1159/000095513. PMID 17053325. S2CID 23553678.
  38. ↑ Monkley SJ, Zhou XH, Kinston SJ, Giblett SM, Hemmings L, Priddle H, Brown JE, Pritchard CA, Critchley DR, Fässler R (Dec 2000). "Disruption of the talin gene arrests mouse development at the gastrulation stage". Developmental Dynamics. 219 (4): 560–74. doi:10.1002/1097-0177(2000)9999:9999<::AID-DVDY1079>3.0.CO;2-Y. PMID 11084655.
  39. 1 2 3 Manso AM, Li R, Monkley SJ, Cruz NM, Ong S, Lao DH, Koshman YE, Gu Y, Peterson KL, Chen J, Abel ED, Samarel AM, Critchley DR, Ross RS (Feb 2013). "Talin1 has unique expression versus talin 2 in the heart and modifies the hypertrophic response to pressure overload". The Journal of Biological Chemistry. 288 (6): 4252–64. doi:10.1074/jbc.M112.427484. PMC 3567677. PMID 23266827.
  40. ↑ Calderwood DA (Feb 2004). "Integrin activation". Journal of Cell Science. 117 (Pt 5): 657–66. doi:10.1242/jcs.01014. PMID 14754902. S2CID 13856948.
  41. ↑ Conti FJ, Felder A, Monkley S, Schwander M, Wood MR, Lieber R, Critchley D, Müller U (Jun 2008). "Progressive myopathy and defects in the maintenance of myotendinous junctions in mice that lack talin 1 in skeletal muscle". Development. 135 (11): 2043–53. doi:10.1242/dev.015818. PMC 2562324. PMID 18434420.
  42. ↑ Nieswandt B, Moser M, Pleines I, Varga-Szabo D, Monkley S, Critchley D, Fässler R (Dec 2007). "Loss of talin1 in platelets abrogates integrin activation, platelet aggregation, and thrombus formation in vitro and in vivo". The Journal of Experimental Medicine. 204 (13): 3113–8. doi:10.1084/jem.20071827. PMC 2150972. PMID 18086864.
  43. ↑ Wegener KL, Basran J, Bagshaw CR, Campbell ID, Roberts GC, Critchley DR, Barsukov IL (Sep 2008). "Structural basis for the interaction between the cytoplasmic domain of the hyaluronate receptor layilin and the talin F3 subdomain". Journal of Molecular Biology. 382 (1): 112–26. doi:10.1016/j.jmb.2008.06.087. PMID 18638481.
  44. ↑ Salgia R, Sattler M, Pisick E, Li JL, Griffin JD (Feb 1996). "p210BCR/ABL induces formation of complexes containing focal adhesion proteins and the protooncogene product p120c-Cbl". Experimental Hematology. 24 (2): 310–3. PMID 8641358.
  45. ↑ Mazaki Y, Hashimoto S, Sabe H (Mar 1997). "Monocyte cells and cancer cells express novel paxillin isoforms with different binding properties to focal adhesion proteins". The Journal of Biological Chemistry. 272 (11): 7437–44. doi:10.1074/jbc.272.11.7437. PMID 9054445.
  46. ↑ Salgia R, Li JL, Lo SH, Brunkhorst B, Kansas GS, Sobhany ES, Sun Y, Pisick E, Hallek M, Ernst T (Mar 1995). "Molecular cloning of human paxillin, a focal adhesion protein phosphorylated by P210BCR/ABL". The Journal of Biological Chemistry. 270 (10): 5039–47. doi:10.1074/jbc.270.10.5039. PMID 7534286.
  47. ↑ Ling K, Doughman RL, Firestone AJ, Bunce MW, Anderson RA (Nov 2002). "Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions". Nature. 420 (6911): 89–93. Bibcode:2002Natur.420...89L. doi:10.1038/nature01082. PMID 12422220. S2CID 4301885.
  48. ↑ Di Paolo G, Pellegrini L, Letinic K, Cestra G, Zoncu R, Voronov S, Chang S, Guo J, Wenk MR, De Camilli P (Nov 2002). "Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin". Nature. 420 (6911): 85–9. Bibcode:2002Natur.420...85D. doi:10.1038/nature01147. PMID 12422219. S2CID 1746983.
  49. ↑ Sun N, Critchley DR, Paulin D, Li Z, Robson RM (May 2008). "Identification of a repeated domain within mammalian alpha-synemin that interacts directly with talin". Experimental Cell Research. 314 (8): 1839–49. doi:10.1016/j.yexcr.2008.01.034. PMID 18342854.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.