Synemin, also known as desmuslin, is a protein that in humans is encoded by the SYNMgene.[5] Synemin is an intermediate filament (IF) family member. IF proteins are cytoskeletal 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, which is a subunit of the IF network, and the extracellular matrix, and provides an important structural support in muscle.
Synemin 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 myofibrils and extracellular matrix. Synemin contributes to linkage between costameres and the contractile apparatus in skeletal muscle of synemin null animals.[6] Synemin plays an important regulatory role in the heart and the consequences of its absence are profound.[7]
Synemin has properties very similar to the intermediate filament syncoilin. 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.[8]
Three splice variant 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.[9]Anintronic sequence of the synemin β isoform is used as a coding sequence for synemin α.[9][10]
The origin of the synemin/desmuslin naming convention is quite complex. In 1980, synemin was first identified in aviansmooth muscle and was initially described as an IF-associated protein due to its colocalization and copurification with desmin and vimentin.[12] 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.[8] 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.[8] In addition, unlike chicken synemin, in vitrocoimmunoprecipitation assays could not detect an interaction between human desmuslin and α-actinin.[8] 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.[9] In 2014 was reported the first synemin -/- null animal.[6]
^ abRotondo JC, Bosi S, Bassi C, Ferracin M, Lanza G, Gafà R, et al. (April 2015). "Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes". Journal of Cellular Physiology. 230 (4): 806–812. doi:10.1002/jcp.24808. hdl:11392/2066612. PMID25205602. S2CID24986454.
^Granger BL, Lazarides E (December 1980). "Synemin: a new high molecular weight protein associated with desmin and vimentin filaments in muscle". Cell. 22 (3): 727–738. doi:10.1016/0092-8674(80)90549-8. PMID7006832. S2CID24349058.
