TLN1

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Talin 1
Protein TLN1 PDB 1mix.png
PDB rendering based on 1mix.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols TLN1 ; ILWEQ; TLN
External IDs OMIM186745 MGI1099832 HomoloGene21267 GeneCards: TLN1 Gene
RNA expression pattern
PBB GE TLN1 203254 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
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 Mb
Chr 4:
43.53 – 43.56 Mb
PubMed search [1] [2]

Talin-1 is a protein that in humans is encoded by the TLN1 gene.[1][2] 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[edit]

Human talin-1 is 270.0 kDa molecular weight and 2541 amino acids.[3] 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.[4][5] In addition to F-actin,[6] the N-terminal region of talin-1 binds layilin,[7] β1- and β3-integrin,[8][9][10] and focal adhesion kinase.[11][12] Talin-1 N-terminal region also binds acidic phospholipids for insertion into lipid bilayers.[13][14][15] The rod domain (>200 kDa) has considerable flexibility and houses a conserved actin binding site,[6] three vinculin binding sites,[16][17][18] and also has an additional integrin binding site, termed IBS2.[19][20][21][22][23] The head and rod domains are connected by an unstructured linker region (residues 401-481), which houses several sites of phosphorylation,[24] as well as protease cleavage.[25] Talin-1 can homodimerize in an antiparallel fashion,[26] however, talin-1 and its closely related counterpart, talin-2 do not form heterodimers.[27]

Function[edit]

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,[28] in correspondence with the I-band and M-line.[29][30][31] Talin-1 is also found at focal adhesions of smooth muscle cells [32] and non-muscle cells.[5]

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.[33] Homozygous disruption of TLN1 in mice is embryonic lethal, demonstrating that talin-1 is required for normal embryogenesis.[34] 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.[35]

The primary function of talin-1 involves the linkage of integrins to the actin cytoskeleton and in the energy-dependent activation of integrins.[5][36] 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.[37] 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.[38] 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.[35]

Clinical significance[edit]

In patients with heart failure, talin-1 expression in cardiomyocytes is increased relative to control cells.[35]

Interactions[edit]

TLN1 has been shown to interact with:

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ "Protein sequence of human TLN1 (Uniprot ID: Q9Y490)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Retrieved 7 July 2015. 
  4. ^ 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. PMID 10970839. 
  5. ^ a b c 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. 
  6. ^ a b c 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". Journal of Cell Science. 109 ( Pt 11): 2715–26. PMID 8937989. 
  7. ^ a b 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. PMID 9786953. 
  8. ^ a b 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. 
  9. ^ a b 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. 
  10. ^ a b 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. PMID 10497155. 
  11. ^ a b 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. 
  12. ^ a b 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. 
  13. ^ 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. PMID 8504857. 
  14. ^ 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. PMID 1510952. 
  15. ^ 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 1061 (2): 121–31. PMID 1900196. 
  16. ^ a b 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 ( Pt 2): 257–63. PMID 10393080. 
  17. ^ a b 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. PMID 8320257. 
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  19. ^ 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. doi:10.1038/320531a0. PMID 2938015. 
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  24. ^ 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. 
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  26. ^ 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. PMID 3108258. 
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Further reading[edit]

  • Luna EJ, Hitt AL (Nov 1992). "Cytoskeleton--plasma membrane interactions". Science 258 (5084): 955–64. doi:10.1126/science.1439807. PMID 1439807. 
  • Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (Jun 2002). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Research 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954. 
  • Critchley DR (Nov 2004). "Cytoskeletal proteins talin and vinculin in integrin-mediated adhesion". Biochemical Society Transactions 32 (Pt 5): 831–6. doi:10.1042/BST0320831. PMID 15494027. 

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