TLN1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTLN1, ILWEQ, TLN, talin 1, talin-1
External IDsOMIM: 186745 MGI: 1099832 HomoloGene: 21267 GeneCards: TLN1
Orthologs
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[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Talin-1 is a protein that in humans is encoded by the TLN1 gene.[5][6] 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.[7] 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.[8][9] In addition to F-actin,[10] the N-terminal region of talin-1 binds layilin,[11] β1- and β3-integrin,[12][13][14] and focal adhesion kinase.[15][16] Talin-1 N-terminal region also binds acidic phospholipids for insertion into lipid bilayers.[17][18][19] The rod domain (>200 kDa) has considerable flexibility and houses a conserved actin binding site,[10] three vinculin binding sites,[20][21][22] and also has an additional integrin binding site, termed IBS2.[23][24][25][26][27] The head and rod domains are connected by an unstructured linker region (residues 401-481), which houses several sites of phosphorylation,[28] as well as protease cleavage.[29] Talin-1 can homodimerize in an antiparallel fashion,[30] however, talin-1 and its closely related counterpart, talin-2 do not form heterodimers.[31]

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,[32] in correspondence with the I-band and M-line.[33][34][35] Talin-1 is also found at focal adhesions of smooth muscle cells [36] and non-muscle cells.[9]

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.[37] Homozygous disruption of TLN1 in mice is embryonic lethal, demonstrating that talin-1 is required for normal embryogenesis.[38] 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.[39]

The primary function of talin-1 involves the linkage of integrins to the actin cytoskeleton and in the energy-dependent activation of integrins.[9][40] 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.[41] 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.[42] 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.[39]

Clinical significance

In patients with heart failure, talin-1 expression in cardiomyocytes is increased relative to control cells.[39]

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.
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  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.
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Further reading

  • Overview of all the structural information available in the PDB for UniProt: Q9Y490 (Human Talin-1) at the PDBe-KB.
  • Overview of all the structural information available in the PDB for UniProt: P26039 (Mouse Talin-1) at the PDBe-KB.

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