TLN1

Talin-1 is a is_associated_with::protein that in humans is encoded by the TLN1 is_associated_with::gene. Talin-1 is ubiquitously expressed, and is localized to is_associated_with::costamere structures in cardiac and is_associated_with::skeletal muscle cells, and to is_associated_with::focal adhesions in is_associated_with::smooth muscle and non-muscle cells. Talin-1 functions to mediate cell-cell adhesion via the linkage of is_associated_with::integrins to the is_associated_with::actin is_associated_with::cytoskeleton and in the activation of is_associated_with::integrins. Altered expression of talin-1 has been observed in patients with is_associated_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 is_associated_with::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 is_associated_with::phospholipids for insertion into is_associated_with::lipid bilayers. The rod domain (>200 kDa) has considerable flexibility and houses a conserved actin binding site, three is_associated_with::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 is_associated_with::phosphorylation, as well as is_associated_with::protease cleavage. Talin-1 can homodimerize in an antiparallel fashion, however, talin-1 and its closely related counterpart, talin-2 do not form is_associated_with::heterodimers.

Function
In mammals talin-1 is ubiquitously expressed; talin-1 is found complexed to integrins and localized to is_associated_with::intercalated discs of is_associated_with::cardiac muscle and to is_associated_with::costamere structures of both skeletal and is_associated_with::cardiac muscles, in correspondence with the I-band and M-line. Talin-1 is also found at is_associated_with::focal adhesions of is_associated_with::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 is_associated_with::embryogenesis. It has been shown, however, that talin-1 expression is minor in adult is_associated_with::cardiomyocytes, and becomes more prominent at is_associated_with::costameres during is_associated_with::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 is_associated_with::skeletal muscle have demonstrated its role in maintaining is_associated_with::integrin attachment sites at myotendinous junctions; knockout mice develop progressive is_associated_with::myopathy and show deficits in muscle force generation. In is_associated_with::platelets, conditional knockout of talin-1 results in the inability to activate is_associated_with::integrins in response to is_associated_with::platelet is_associated_with::agonists, resulting in mice with severe hemostatic defects and resistance to arterial is_associated_with::thrombosis. Conditional knockout of talin-1 in is_associated_with::cardiomyocytes shows that mice have normal cardiac function at baseline, but improved function, blunted hypertrophy, and attenuated fibrosis when subjected to pressure overload-induced is_associated_with::cardiac hypertrophy, which correlated with blunted ERK1/2, p38, is_associated_with::Akt, and is_associated_with::glycogen synthase kinase 3 responses. These data suggest that upregulation of talin-1 in is_associated_with::cardiac hypertrophy may be detrimental to is_associated_with::cardiomyocytes function.

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

Interactions
TLN1 has been shown to interact with:


 * is_associated_with::ACTA1,
 * is_associated_with::CD61,
 * is_associated_with::ITGB1,
 * is_associated_with::LAYN,
 * PXN,
 * is_associated_with::PIP5K1C,
 * is_associated_with::PTK2,
 * is_associated_with::SYNM, and
 * VCL.