Talin-1 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''TLN1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. Talin-1 is ubiquitously expressed, and is localized to

costamere The costamere is a structural-functional component of striated muscle cells which connects the sarcomere of the muscle to the cell membrane (i.e. the sarcolemma).20: 2327-2331 Costameres are sub-sarcolemmal protein assemblies circumferentially a ...

structures in

cardiac The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...

and

skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

cells, and to

focal adhesion In cell biology, focal adhesions (also cell–matrix adhesions or FAs) are large macromolecular assemblies through which mechanical force and regulatory signals are transmitted between the extracellular matrix (ECM) and an interacting cell. More ...

s in

smooth muscle Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

and non-muscle cells. Talin-1 functions to mediate cell-cell adhesion via the linkage of

integrins Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...

to the

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

and in the activation of

. Altered expression of talin-1 has been observed in patients with

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

, 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 The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

region of talin-1 is ~50 kDa in size and homologous to members of the

ERM protein family The ERM protein family consists of three closely related proteins, ezrin, radixin and moesin. The three paralogs, ezrin, radixin and moesin, are present in vertebrates, whereas other species have only one ERM gene. Therefore, in vertebrates these ...

which have a globular

FERM domain In molecular biology, the FERM domain (F for 4.1 protein, E for ezrin, R for radixin and M for moesin) is a widespread protein module involved in localising proteins to the plasma membrane. FERM domains are found in a number of cytoskeletal-ass ...

(residues 86-400) that links the actin cytoskeleton to adhesion proteins. In addition to

F-actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ov ...

, the

region of talin-1 binds layilin, β1- and β3-integrin, and

focal adhesion kinase PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by the ''PTK2'' gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion (how cells stick to ...

. Talin-1

region also binds acidic

phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

s for insertion into

lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...

s. The rod domain (>200 kDa) has considerable flexibility and houses a conserved actin binding site, three

vinculin In mammalian cells, vinculin is a membrane-cytoskeletal protein in focal adhesion plaques that is involved in linkage of integrin adhesion molecules to the actin cytoskeleton. Vinculin is a cytoskeletal protein associated with cell-cell and cell ...

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

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

, as well as

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...

cleavage. Talin-1 can

homodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' ha ...

ize in an antiparallel fashion, however, talin-1 and its closely related counterpart, talin-2 do not form

heterodimer In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

Function

In mammals talin-1 is ubiquitously expressed; talin-1 is found complexed to integrins and localized to

intercalated disc Intercalated discs or lines of Eberth are microscopic identifying features of cardiac muscle. Cardiac muscle consists of individual heart muscle cells (cardiomyocytes) connected by intercalated discs to work as a single functional syncytium. By con ...

s of

cardiac muscle Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...

and to

structures of both

skeletal A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...

and

s, in correspondence with the

I-band The NATO I band is the obsolete designation given to the radio frequencies from 8 000 to 10 000 MHz (equivalent to wavelengths between 3.75 and 3 cm) during the Cold War period. Since 1992 frequency allocations, allotment and assignments are ...

and

M-line M line may refer to: *M-line (mittel line or middle line), a structure in a muscle sarcomere *M Ocean View, a light rail and former streetcar line in San Francisco, California *McKinney Avenue Transit Authority, a streetcar line in Dallas, Texas al ...

. Talin-1 is also found at

s of

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

embryogenesis An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sperm ...

. It has been shown, however, that talin-1 expression is minor in adult

cardiomyocyte Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...

s, and becomes more prominent at

s during 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

have demonstrated its role in maintaining

integrin Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...

attachment sites at

myotendinous junction Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...

s; knockout mice develop progressive

myopathy In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...

and show deficits in muscle force generation. In

platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

s, conditional knockout of talin-1 results in the inability to activate

in response to

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

s, resulting in mice with severe hemostatic defects and resistance to arterial

thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thro ...

. Conditional knockout of talin-1 in

s 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 Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, tran ...

, and glycogen synthase kinase 3 responses. These data suggest that upregulation of talin-1 in cardiac hypertrophy may be detrimental to

s function.

Clinical significance

In patients with

, talin-1 expression in

s is increased relative to control cells.

Interactions

TLN1 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

ACTA1 Actin, alpha skeletal muscle is a protein that in humans is encoded by the ''ACTA1'' gene. Actin alpha 1 which is expressed in skeletal muscle is one of six different actin isoforms which have been identified. Actins are highly conserved proteins ...

, *

CD61 Integrin beta-3 (β3) or CD61 is a protein that in humans is encoded by the ''ITGB3'' gene. CD61 is a cluster of differentiation found on thrombocytes. Structure and function The ITGB3 protein product is the integrin beta chain beta 3. Integrins ...

, *

ITGB1 Integrin beta-1 (ITGB1), also known as CD29, is a cell surface receptor that in humans is encoded by the ''ITGB1'' gene. This integrin associates with integrin alpha 1 and integrin alpha 2 to form integrin complexes which function as collagen r ...

, *

LAYN Torah reading (; ') is a Judaism, Jewish religion, religious tradition that involves the public reading of a set of passages from a Sefer Torah, Torah scroll. The term often refers to the entire ceremony of removing the scroll (or scrolls) fro ...

, *

PXN Paxillin is a protein that in humans is encoded by the ''PXN'' gene. Paxillin is expressed at focal adhesions of non-striated cells and at costameres of striated muscle cells, and it functions to adhere cells to the extracellular matrix. Mutation ...

, * PIP5K1C, *

PTK2 PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by the ''PTK2'' gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion (how cells stick to ...

, *

SYNM Synemin, also known as desmuslin, is a protein that in humans is encoded by the ''SYNM'' gene. Synemin is an intermediate filament (IF) family member. IF proteins are cytoskeletal proteins that confer resistance to mechanical stress and are encode ...

, and * VCL.

References

External links

* * {{NLM content