Synemin, also known as desmuslin, is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

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

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. Synemin is an

intermediate filament Intermediate filaments (IFs) are cytoskeleton, cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate ''Branchiostoma' ...

(IF) family member. IF proteins are

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

proteins that confer resistance to mechanical stress and are encoded by a dispersed multigene family. This protein has been found to form a linkage between

desmin Desmin is a protein that in humans is encoded by the ''DES'' gene. Desmin is a muscle-specific, type III intermediate filament that integrates the sarcolemma, Z disk, and nuclear membrane in sarcomeres and regulates sarcomere architecture. ...

, which is a subunit of the IF network, and the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

, and provides an important structural support in muscle.

Function

Synemin is an

(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 A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal striated muscle, Skeletal muscles are composed of tubular ...

of skeletal myocytes. It localizes at the Z-disk and has been shown to bind to α-dystrobrevin, α-actinin, and

to act as a mechanical linker in transmitting

force In physics, a force is an influence that can cause an Physical object, object to change its velocity unless counterbalanced by other forces. In mechanics, force makes ideas like 'pushing' or 'pulling' mathematically precise. Because the Magnitu ...

laterally throughout the tissue, especially between the contractile

myofibril A myofibril (also known as a muscle fibril or sarcostyle) is a basic rod-like organelle of a muscle cell. Skeletal muscles are composed of long, tubular cells known as Skeletal muscle#Skeletal muscle cells, muscle fibers, and these cells contain ...

s and extracellular matrix. Synemin contributes to linkage between costameres and the contractile apparatus in skeletal muscle of synemin null animals. Synemin plays an important regulatory role in the heart and the consequences of its absence are profound.

Properties

Synemin has properties very similar to the intermediate filament

syncoilin Discovery Syncoilin is a muscle-specific atypical Intermediate filament#Type III, type III intermediate filament protein encoded in the human by the gene ''SYNC''. It was first isolated as a binding partner to DTNA, α-dystrobrevin, as determine ...

. In particular, it binds to α-dystrobrevin in the

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 costa ...

-associated protein complex to act as a mechanical "linker" between the myofibrillar network and the cell membrane.

Splice variants

Three

splice variant Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene may be included ...

isoforms of synemin exist, α and β and L. 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

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...

ic sequence of the synemin β isoform is used as a coding sequence for synemin α.

Cancer

SYNM gene has been observed progressively downregulated in

Human papillomavirus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and r ...

-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy. For this reason, SYNM is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression.

History

The origin of the synemin/desmuslin naming convention is quite complex. In 1980, synemin was first identified in avian

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

and was initially described as an IF-associated protein due to its colocalization and copurification with

and

vimentin Vimentin is a structural protein that in humans is encoded by the ''VIM'' gene. Its name comes from the Latin ''vimentum'' which refers to an array of flexible rods. Vimentin is a Intermediate filament#Type III, type III intermediate filamen ...

. Subsequent to the

cloning Cloning is the process of producing individual organisms with identical genomes, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction; this reproduction of an organism by itself without ...

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 acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

sequence of chicken synemin, while the IF proteins

and

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. In 2014 was reported the first synemin -/- null animal.

References

External links

* {{NLM content