Synemin
Encyclopedia
Synemin, also called desmuslin, is an intermediate filament
(IF) and, like other IFs, primarily functions to integrate mechanical stress and maintain structural integrity in eukaryotic cells. While it has been observed in a variety of cell types, it has been best studied in the sarcomere
of skeletal myocytes. It localizes at the Z-disk and has been shown to bind to α-dystrobrevin, α-actinin, and desmin
to act as a mechanical linker in transmitting force
laterally throughout the tissue, especially between the contractile myofibril
s and extracellular matrix.
. In particular, it binds to α-dystrobrevin in the dystrophin
-associated protein complex to act as a mechanical "linker" between the myofibrillar network and the cell membrane.
ic sequence of the synemin β isoform is used as a coding sequence for synemin α.
smooth muscle
and was initially described as an IF-associated protein due to its colocalization and copurification with desmin
and vimentin
. Subsequent to the cloning
of chicken synemin, Mizuno and colleagues reported the cloning of a novel IF protein, human desmuslin, as an α-dystrobrevin-interacting protein. Sequence analysis showed that human desmuslin was 32% identical and 11% similar to the amino acid
sequence of chicken synemin, while the IF proteins vimentin
and desmin
are more than 80% identical across the same species. Although several parts were very similar between human desmuslin and chicken synemin, the low degree of conservation between these two proteins compared to other cloned IF proteins suggested that synemin was not the human desmuslin orthologue. In addition, unlike chicken synemin, in vitro coimmunoprecipitation assays could not detect an interaction between human desmuslin and α-actinin. In 2001, Titeux and colleagues reported the cloning of the α and β splice-varying isoforms of human synemin and showed that β-synemin was identical to desmuslin.
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...
(IF) and, like other IFs, primarily functions to integrate mechanical stress and maintain structural integrity in eukaryotic cells. While it has been observed in a variety of cell types, it has been best studied in 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...
of skeletal myocytes. It localizes at the Z-disk and has been shown to bind to α-dystrobrevin, α-actinin, and desmin
Desmin
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 sarcomeres. 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...
to act as a mechanical linker in transmitting force
Force
In physics, a force is any influence that causes an object to undergo a change in speed, a change in direction, or a change in shape. In other words, a force is that which can cause an object with mass to change its velocity , i.e., to accelerate, or which can cause a flexible object to deform...
laterally throughout the tissue, especially between the contractile 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 and extracellular matrix.
Properties
Synemin has properties very similar to the intermediate filament syncoilinSyncoilin
Syncoilin is a muscle-specific intermediate filament, first isolated as a binding partner to α-dystrobrevin, as determined by a yeast two-hybrid assay.Later, a yeast two-hybrid method was used to demonstrate that syncoilin is a binding partner of desmin...
. In particular, it binds to α-dystrobrevin in the dystrophin
Dystrophin
Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costamere or the dystrophin-associated protein complex...
-associated protein complex to act as a mechanical "linker" between the myofibrillar network and the cell membrane.
Splice Variants
Two splice variant isoforms of synemin exist, α and β. Both isoforms have a very short N-terminal domain of 10 amino acids and a long C-terminal domain consisting of 1243 amino acids for the α isoform and 931 amino acids for the β isoform. An intronIntron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
ic sequence of the synemin β isoform is used as a coding sequence for synemin α.
History
The origin of the synemin/desmuslin naming convention is quite complex. In 1980, synemin was first identified in avianBird
Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
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...
and was initially described as an IF-associated protein due to its colocalization and copurification with desmin
Desmin
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 sarcomeres. 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...
and 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...
. Subsequent to the cloning
Cloning
Cloning in biology is the process of producing similar populations of genetically identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or...
of chicken synemin, Mizuno and colleagues reported the cloning of a novel IF protein, human desmuslin, as an α-dystrobrevin-interacting protein. Sequence analysis showed that human desmuslin was 32% identical and 11% similar to the 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...
sequence of chicken synemin, while the IF proteins 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...
and desmin
Desmin
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 sarcomeres. 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...
are more than 80% identical across the same species. Although several parts were very similar between human desmuslin and chicken synemin, the low degree of conservation between these two proteins compared to other cloned IF proteins suggested that synemin was not the human desmuslin orthologue. In addition, unlike chicken synemin, in vitro coimmunoprecipitation assays could not detect an interaction between human desmuslin and α-actinin. In 2001, Titeux and colleagues reported the cloning of the α and β splice-varying isoforms of human synemin and showed that β-synemin was identical to desmuslin.