TLN1

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]

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]

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

TLN1 has been shown to interact with:

• Talin protein

• 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.

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