Phospholamban
Encyclopedia
Phospholamban, also known as PLN, is a protein
that in humans is encoded by the PLN gene
. Phospholamban is a 52-amino acid
integral membrane protein
that regulates the Ca2+
pump in cardiac muscle
and skeletal muscle
cells.
of the protein. The subsequent activation of the Ca++ pump leads to shorter intervals between contractions, thereby contributing to the lusitropic response elicited in heart by beta-agonists. The protein is a key regulator of . Mutations in this gene are a cause of inherited human dilated cardiomyopathy
with refractory congestive heart failure
.
When phospholamban is phosphorylated by its ability to inhibit the sarcoplasmic reticulum calcium pump (SERCA) is lost. Thus, activators of PKA, such as the beta-adrenergic agonist epinephrine
(released by sympathetic
stimulation), may enhance the rate of cardiac myocyte relaxation. In addition, since SERCA is more active, the next action potential
will cause an increased release of calcium, resulting in increased contraction (positive inotropic effect). When phospholamban is not phosphorylated, such as when PKA is inactive, it can interact with and inhibit SERCA. The overall effect of phospholamban is to decrease the rate of and , thereby decreasing heart rate and stroke volume, respectively.
Mutations in this gene are a cause of inherited human dilated with refractory .
with SLN and ATP2A1
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the PLN gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Phospholamban is a 52-amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
integral membrane protein
Integral membrane protein
An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...
that regulates the Ca2+
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
pump in 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...
and 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...
cells.
Function
The protein encoded by this gene is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase in cardiac muscle. The protein is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca++-ATPase in the unphosphorylated state, but inhibition is relieved upon phosphorylationPhosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
of the protein. The subsequent activation of the Ca++ pump leads to shorter intervals between contractions, thereby contributing to the lusitropic response elicited in heart by beta-agonists. The protein is a key regulator of . Mutations in this gene are a cause of inherited human dilated cardiomyopathy
Dilated cardiomyopathy
Dilated cardiomyopathy or DCM is a condition in which the heart becomes weakened and enlarged and cannot pump blood efficiently. The decreased heart function can affect the lungs, liver, and other body systems....
with refractory congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
.
When phospholamban is phosphorylated by its ability to inhibit the sarcoplasmic reticulum calcium pump (SERCA) is lost. Thus, activators of PKA, such as the beta-adrenergic agonist epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
(released by sympathetic
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
stimulation), may enhance the rate of cardiac myocyte relaxation. In addition, since SERCA is more active, the next 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...
will cause an increased release of calcium, resulting in increased contraction (positive inotropic effect). When phospholamban is not phosphorylated, such as when PKA is inactive, it can interact with and inhibit SERCA. The overall effect of phospholamban is to decrease the rate of and , thereby decreasing heart rate and stroke volume, respectively.
Clinical significance
Gene knockout of phospholamban results in animals with hyperdynamic hearts, with little apparent negative consequence.Mutations in this gene are a cause of inherited human dilated with refractory .
Interactions
PLN (gene) has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with SLN and ATP2A1
ATP2A1
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 is an enzyme that in humans is encoded by the ATP2A1 gene.-Interactions:ATP2A1 has been shown to interact with PLN and SLN.-Further reading:...
.