TLN1

TLN1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1SYQ, 2MWN, 4DJ9
Identifiers
Aliases	TLN1, ILWEQ, TLN, talin 1
External IDs	MGI: 1099832 HomoloGene: 21267 GeneCards: TLN1
Gene ontology Molecular function • structural constituent of cytoskeleton • actin filament binding • LIM domain binding • integrin binding • protein binding • vinculin binding • protein complex binding • actin binding • cadherin binding involved in cell-cell adhesion Cellular component • cytoskeleton • cell projection • ruffle membrane • microtubule organizing center • ruffle • cytosol • extracellular exosome • membrane • cell surface • plasma membrane • cytoplasm • cell-cell junction • cell junction • focal adhesion • extracellular region • cell-cell adherens junction Biological process • cell-substrate junction assembly • IRE1-mediated unfolded protein response • muscle contraction • platelet degranulation • movement of cell or subcellular component • platelet aggregation • cell-cell junction assembly • cortical actin cytoskeleton organization • cytoskeletal anchoring at plasma membrane • cell adhesion • viral process Sources:Amigo / QuickGO
RNA expression pattern
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_006280.3	NP_035732.2
Location (UCSC)	Chr 9: 35.7 – 35.73 Mb	Chr 4: 43.53 – 43.56 Mb
PubMed search	[1]	[2]
Wikidata

Talin-1 is a protein that in humans is encoded by the TLN1 gene.^[3][4] 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.^[5] 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.^[6][7] In addition to F-actin,^[8] the N-terminal region of talin-1 binds layilin,^[9] β1- and β3-integrin,^[10][11][12] and focal adhesion kinase.^[13][14] Talin-1 N-terminal region also binds acidic phospholipids for insertion into lipid bilayers.^[15][16][17] The rod domain (>200 kDa) has considerable flexibility and houses a conserved actin binding site,^[8] three vinculin binding sites,^[18][19][20] and also has an additional integrin binding site, termed IBS2.^{[21][22][23][24][25]} The head and rod domains are connected by an unstructured linker region (residues 401-481), which houses several sites of phosphorylation,^[26] as well as protease cleavage.^[27] Talin-1 can homodimerize in an antiparallel fashion,^[28] however, talin-1 and its closely related counterpart, talin-2 do not form heterodimers.^[29]

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,^[30] in correspondence with the I-band and M-line.^[31][32][33] Talin-1 is also found at focal adhesions of smooth muscle cells ^[34] and non-muscle cells.^[7]

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.^[35] Homozygous disruption of TLN1 in mice is embryonic lethal, demonstrating that talin-1 is required for normal embryogenesis.^[36] 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.^[37]

The primary function of talin-1 involves the linkage of integrins to the actin cytoskeleton and in the energy-dependent activation of integrins.^[7][38] 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.^[39] 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.^[40] 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.^[37]

Clinical significance

In patients with heart failure, talin-1 expression in cardiomyocytes is increased relative to control cells.^[37]

Interactions

TLN1 has been shown to interact with:

See also

• Talin protein

References

Further reading

PDB gallery
1mix: Crystal structure of a FERM domain of Talin  1miz: Crystal structure of an integrin beta3-talin chimera  1mk7: CRYSTAL STRUCTURE OF AN INTEGRIN BETA3-TALIN CHIMERA  1mk9: CRYSTAL STRUCTURE OF AN INTEGRIN BETA3-TALIN CHIMERA  1sj7: Crystal Structure of Talin Rod 482-655  1sj8: Crystal Structure of talin residues 482-789  1u89: Solution structure of VBS2 fragment of talin  1y19: Structural basis for phosphatidylinositol phosphate kinase type I-gamma binding to talin at focal adhesions  2b0h: Solution structure of VBS3 fragment of talin  2g35: NMR structure of talin-PTB in complex with PIPKI  2h7d: Solution structure of the talin F3 domain in complex with a chimeric beta3 integrin-PIP kinase peptide  2h7e: Solution structure of the talin F3 domain in complex with a chimeric beta3 integrin-PIP kinase peptide- minimized average structure

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