Troponin
Encyclopedia
Troponin is a complex of three regulatory proteins (troponin C, troponin I and troponin T) that is integral to muscle contraction
in skeletal
and cardiac muscle
, but not smooth muscle
.
Discussions of troponin often pertain to its functional characteristics and/or to its usefulness as a diagnostic marker for various heart disorders.
and lies within the groove between actin
filaments in muscle tissue. In a relaxed muscle, tropomyosin blocks the attachment site for the myosin
crossbridge, thus preventing contraction. When the muscle cell is stimulated to contract by an action potential
, calcium channels open in the sarcoplasmic membrane and release calcium into the sarcoplasm. Some of this calcium attaches to troponin which causes it to change shape, exposing binding sites for myosin (active sites) on the actin
filaments
. Myosin
binding to actin forms cross bridges and contraction (cross bridge cycling) of the muscle begins.
Troponin is found in both skeletal muscle
and cardiac muscle, but the specific versions of troponin differ between types of muscle. The main difference is that the TnC subunit of troponin in skeletal muscle has four calcium ion binding sites, whereas in cardiac muscle there are only three. The actual amount of calcium that binds to troponin varies from expert to expert and source to source.
concentration. When calcium rises, the muscles contract, and when calcium falls, the muscles relax.
Troponin is a component of thin filaments (along with actin
and tropomyosin
), and is the protein to which calcium binds to accomplish this regulation. Troponin has three subunits, TnC, TnI, and TnT. When calcium is bound to specific sites on TnC, tropomyosin
rolls out of the way of the actin filament active sites, so that myosin
(a molecular motor organized in muscle thick filaments) can attach to the thin filament and produce force and/or movement. In the absence of calcium, tropomyosin interferes with this action of myosin, and therefore muscles remain relaxed.
Troponin I has also been shown to inhibit angiogenesis
in vivo
and in vitro
.
Individual subunits serve different functions:
Smooth muscle does not have troponin.
.
.
Muscle contraction
Muscle fiber generates tension through the action of actin and myosin cross-bridge cycling. While under tension, the muscle may lengthen, shorten, or remain the same...
in skeletal
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
and cardiac muscle
Cardiac muscle
Cardiac muscle is a type of involuntary striated muscle found in the walls and histologic foundation of the heart, specifically the myocardium. Cardiac muscle is one of three major types of muscle, the others being skeletal and smooth muscle...
, but not smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
.
Discussions of troponin often pertain to its functional characteristics and/or to its usefulness as a diagnostic marker for various heart disorders.
Function
Troponin is attached to the protein tropomyosinTropomyosin
Tropomyosin is an actin-binding protein that regulates actin mechanics. It is important, among other things, for muscle contraction. Tropomyosin, along with the troponin complex, associate with actin in muscle fibers and regulate muscle contraction by regulating the binding of myosin...
and lies within the groove between actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
filaments in muscle tissue. In a relaxed muscle, tropomyosin blocks the attachment site for the myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
crossbridge, thus preventing contraction. When the muscle cell is stimulated to contract by an action potential
Action potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
, calcium channels open in the sarcoplasmic membrane and release calcium into the sarcoplasm. Some of this calcium attaches to troponin which causes it to change shape, exposing binding sites for myosin (active sites) on the actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
filaments
Protein filament
In biology, a filament is a "long chain of proteins, such as those found in hair, muscle, or in flagella". They are often bundled together for strength and rigidity. Some cellular examples include:*Actin filaments*Microtubules*Intermediate filaments...
. Myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
binding to actin forms cross bridges and contraction (cross bridge cycling) of the muscle begins.
Troponin is found in both skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
and cardiac muscle, but the specific versions of troponin differ between types of muscle. The main difference is that the TnC subunit of troponin in skeletal muscle has four calcium ion binding sites, whereas in cardiac muscle there are only three. The actual amount of calcium that binds to troponin varies from expert to expert and source to source.
Physiology
Both cardiac and skeletal muscles are controlled by changes in the intracellular calciumCalcium in biology
Calcium plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization...
concentration. When calcium rises, the muscles contract, and when calcium falls, the muscles relax.
Troponin is a component of thin filaments (along with actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
and tropomyosin
Tropomyosin
Tropomyosin is an actin-binding protein that regulates actin mechanics. It is important, among other things, for muscle contraction. Tropomyosin, along with the troponin complex, associate with actin in muscle fibers and regulate muscle contraction by regulating the binding of myosin...
), and is the protein to which calcium binds to accomplish this regulation. Troponin has three subunits, TnC, TnI, and TnT. When calcium is bound to specific sites on TnC, tropomyosin
Tropomyosin
Tropomyosin is an actin-binding protein that regulates actin mechanics. It is important, among other things, for muscle contraction. Tropomyosin, along with the troponin complex, associate with actin in muscle fibers and regulate muscle contraction by regulating the binding of myosin...
rolls out of the way of the actin filament active sites, so that myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
(a molecular motor organized in muscle thick filaments) can attach to the thin filament and produce force and/or movement. In the absence of calcium, tropomyosin interferes with this action of myosin, and therefore muscles remain relaxed.
Troponin I has also been shown to inhibit angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
and in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
.
Individual subunits serve different functions:
- Troponin CTroponin CTroponin C is a part of the troponin complex. It contains four calcium-binding EF hands. It is a component of thin filaments . It contains an N lobe and a C lobe. The C lobe serves a structural purpose and binds to the N domain of TnI. The C lobe can bind either Ca2+ or Mg2+...
binds to calcium ions to produce a conformational change in TnI - Troponin TTroponin TTroponin T is a part of the troponin complex. It binds to tropomyosin, interlocking them to form a troponin-tropomyosin complex.The tissue specific subtypes are:* Slow skeletal troponin T1, TNNT1 * Cardiac troponin T2, TNNT2...
binds to tropomyosin, interlocking them to form a troponin-tropomyosin complex - Troponin ITroponin ITroponin I is a part of the troponin complex. It binds to actin in thin myofilaments to hold the actin-tropomyosin complex in place. Because of it myosin cannot bind actin in relaxed muscle...
binds to actin in thin myofilaments to hold the troponin-tropomyosin complex in place
Smooth muscle does not have troponin.
Diagnostic use
Troponin levels can be used as a test of several different heart disorders, including myocardial infarctionMyocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
.
Relation with contractile function and heart failure
Mutations in the cardiac troponin subunits can result in cardiomyopathies, including familial hypertrophic cardiomyopathyHypertrophic cardiomyopathy
Hypertrophic cardiomyopathy is a disease of the myocardium in which a portion of the myocardium is hypertrophied without any obvious cause...
.