Desmin
Encyclopedia
Desmin is a protein
that in humans is encoded by the DES gene
.
Desmin is a type III intermediate filament
found near the Z line in sarcomere
s. It was first described in 1976, first purified in 1977, the gene
was cloned in 1989, and the first knock-out mouse was created in 1996. Desmin is only expressed in vertebrates, however homologous proteins are found in many organisms. It is a 52kD protein that is a subunit of intermediate filaments in skeletal muscle
tissue, smooth muscle
tissue, and cardiac muscle
tissue.
Desmin is one of the earliest protein markers for muscle tissue in embryogenesis as it is detected in the somite
s of myoblast
s. Although it is present early in the development of muscle cells it is expressed at low levels and increases as the cell nears terminal differentiation the muscle cell matures only desmin is present. A similar protein, vimentin
, is present in higher amounts during embryogenesis while desmin is present in higher amounts after differentiation. This suggests that there may be some interaction between the two in determining muscle cell differentiation. However desmin knockout mice develop normally and only experience defects later in life. Since desmin is expressed at a low level during differentiation another protein may be able to compensate for desmin's function early in development but not later on.
Desmin is also important in muscle cell architecture and structure since it connects many components of the cytoplasm
. The sarcomere
is a component of muscle cells composed of filaments and myosin
motor proteins which allow the cell to contract. Desmin forms a scaffold around the Z-disk of the sarcomere and connects the Z-disk to the subsarcolemmal
cytoskeleton (the cytoplasmic part of the muscle cell plasma membrane). It links the myofibril
s laterally by connecting the Z-disks. Through its connection to the sarcomere Desmin connects the contractile apparatus to the cell nucleus
, mitochondria, and post-synaptic areas of motor endplates. These connections maintain the structural and mechanical integrity of the cell during contraction while also helping in force transmission and longitudinal load bearing. There is some evidence that desmin may also connect the sarcomere to the extracellular matrix
(ECM) through desmosomes which could be important in signalling between the ECM and the sarcomere which could regulate muscle contraction and movement.
Finally, desmin may be important in mitochondria function. When desmin is not functioning properly there is improper mitochondrial distribution, number, morphology and function. Since desmin links the mitochondria to the sarcomere it may transmit information about contractions and energy need and through this regulate the aerobic respiration rate of the muscle cell.
and heart
are affected. The mice without desmin are weaker and fatigue more easily than wild type mice and the muscle fibers are more likely to be damaged during contraction, presumably because the desmin is responsible for keeping the muscle fibers aligned. Mice without desmin also have impaired mitochondrial function.
s, instead forming aggregates of desmin and other proteins throughout the cell.
It is also associated with Sarcoma botryoides
(rhabdomyosarcoma variant) - a spindle-shaped vaginal carcinoma that affects girls < 4 years of age.
rod, a variable non alpha helix head, and a carboxy-terminal tail. Desmin, as all intermediate filaments, shows no polarity when assembled. The rod domain consists of 308 amino acids with parallel alpha helical coiled coil dimers and three linkers to disrupt it. The rod connects to the head domain. The head domain 84 amino acids with many arginine, serine, and aromatic residues is important in filament assembly and dimer-dimer interactions. The tail domain is responsible for the integration of filaments and interaction with proteins and organelles.
with Desmoplakin
.
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 DES 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...
.
Desmin is a type III intermediate filament
Intermediate filament
Intermediate filaments are a family of related proteins that share common structural and sequence features. Intermediate filaments have an average diameter of 10 nanometers, which is between that of 7 nm actin , and that of 25 nm microtubules, although they were initially designated...
found near the Z line in sarcomere
Sarcomere
A sarcomere is the basic unit of a muscle. Muscles are composed of tubular muscle cells . Muscle cells are composed of tubular myofibrils. Myofibrils are composed of repeating sections of sarcomeres, which appear under the microscope as dark and light bands...
s. It was first described in 1976, first purified in 1977, the 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...
was cloned in 1989, and the first knock-out mouse was created in 1996. Desmin is only expressed in vertebrates, however homologous proteins are found in many organisms. It is a 52kD protein that is a subunit of intermediate filaments in 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...
tissue, 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...
tissue, 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...
tissue.
Putative functions
The function of desmin has been deduced through studies in knockout mice, but the underlying mechanism of its action is not known. These possibilities may be the result of interactions with other proteins and not desmin itself. More research needs to be done on desmin's expression and interactions in the muscle cell in order to determine its exact function.Desmin is one of the earliest protein markers for muscle tissue in embryogenesis as it is detected in the somite
Somite
A somite is a division of the body of an animal. In vertebrates this is mainly discernible in the embryo stage; in arthropods it is a characteristic of a hypothetical ancestor.- In vertebrates :...
s of myoblast
Myoblast
A myoblast is a type of embryonic progenitor cell that gives rise to muscle cells .The muscle cells can be skeletal muscle, smooth muscle, and cardiac muscle....
s. Although it is present early in the development of muscle cells it is expressed at low levels and increases as the cell nears terminal differentiation the muscle cell matures only desmin is present. A similar protein, vimentin
Vimentin
Vimentin is a type III intermediate filament protein that is expressed in mesenchymal cells. IF proteins are found in all metazoan cells as well as bacteria. IF, along with tubulin-based microtubules and actin-based microfilaments, comprise the cytoskeleton...
, is present in higher amounts during embryogenesis while desmin is present in higher amounts after differentiation. This suggests that there may be some interaction between the two in determining muscle cell differentiation. However desmin knockout mice develop normally and only experience defects later in life. Since desmin is expressed at a low level during differentiation another protein may be able to compensate for desmin's function early in development but not later on.
Desmin is also important in muscle cell architecture and structure since it connects many components of the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
. The sarcomere
Sarcomere
A sarcomere is the basic unit of a muscle. Muscles are composed of tubular muscle cells . Muscle cells are composed of tubular myofibrils. Myofibrils are composed of repeating sections of sarcomeres, which appear under the microscope as dark and light bands...
is a component of muscle cells composed of filaments and 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...
motor proteins which allow the cell to contract. Desmin forms a scaffold around the Z-disk of the sarcomere and connects the Z-disk to the subsarcolemmal
Sarcolemma
The sarcolemma is the cell membrane of a muscle cell . It consists of a true cell membrane, called the plasma membrane, and an outer coat made up of a thin layer of polysaccharide material that contains numerous thin collagen fibrils...
cytoskeleton (the cytoplasmic part of the muscle cell plasma membrane). It links the myofibril
Myofibril
A myofibril is a basic unit of a muscle. Muscles are composed of tubular cells called myocytes or myofibers. Myofibers are composed of tubular myofibrils. Myofibrils are composed of long proteins such as actin, myosin, and titin, and other proteins that hold them together...
s laterally by connecting the Z-disks. Through its connection to the sarcomere Desmin connects the contractile apparatus to the cell nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, mitochondria, and post-synaptic areas of motor endplates. These connections maintain the structural and mechanical integrity of the cell during contraction while also helping in force transmission and longitudinal load bearing. There is some evidence that desmin may also connect the sarcomere to the extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
(ECM) through desmosomes which could be important in signalling between the ECM and the sarcomere which could regulate muscle contraction and movement.
Finally, desmin may be important in mitochondria function. When desmin is not functioning properly there is improper mitochondrial distribution, number, morphology and function. Since desmin links the mitochondria to the sarcomere it may transmit information about contractions and energy need and through this regulate the aerobic respiration rate of the muscle cell.
Knockout phenotype
When the gene for desmin is knocked out it is no longer able to function properly. Mice with the desmin knockout gene develop normally and are fertile, however soon after birth they begin to show defects in skeletal, smooth and cardiac muscle; in particular the diaphragmThoracic diaphragm
In the anatomy of mammals, the thoracic diaphragm, or simply the diaphragm , is a sheet of internal skeletal muscle that extends across the bottom of the rib cage. The diaphragm separates the thoracic cavity from the abdominal cavity and performs an important function in respiration...
and heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
are affected. The mice without desmin are weaker and fatigue more easily than wild type mice and the muscle fibers are more likely to be damaged during contraction, presumably because the desmin is responsible for keeping the muscle fibers aligned. Mice without desmin also have impaired mitochondrial function.
Associated diseases
Desmin Related Myopathy (DRM or Desminopathy) is a subgroup of the myofibrillar myopathy diseases and is the result of a mutation in the gene that codes for desmin which prevents it from forming protein filamentProtein 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...
s, instead forming aggregates of desmin and other proteins throughout the cell.
It is also associated with Sarcoma botryoides
Sarcoma botryoides
Sarcoma botryoides or botryoid sarcoma or botryoid rhabdomyosarcoma is a subtype of embryonal rhabdomyosarcoma, that can be observed in the walls of hollow, mucosa lined structures such as the nasopharynx, common bile duct, urinary bladder of infants and young children or the vagina in females,...
(rhabdomyosarcoma variant) - a spindle-shaped vaginal carcinoma that affects girls < 4 years of age.
Structure
There are three major domains to this protein: a conserved alpha helixAlpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
rod, a variable non alpha helix head, and a carboxy-terminal tail. Desmin, as all intermediate filaments, shows no polarity when assembled. The rod domain consists of 308 amino acids with parallel alpha helical coiled coil dimers and three linkers to disrupt it. The rod connects to the head domain. The head domain 84 amino acids with many arginine, serine, and aromatic residues is important in filament assembly and dimer-dimer interactions. The tail domain is responsible for the integration of filaments and interaction with proteins and organelles.
Interactions
Desmin 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 Desmoplakin
Desmoplakin
Desmoplakin is a protein associated with desmosomes.Desmoplakin is a protein that in humans is encoded by the DSP gene. The C-terminus of desmoplakin binds with intermediate filaments. These are further sub divided to three homologous Plakin repeat domains . In the mid-region of desmoplakin, a...
.
External links
- GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy
- LOVD mutation database: DES