|Symbols||; CSM1; CSM2|
|RNA expression pattern|
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 knockout 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.
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 somites. Although it is present early in the development of muscle cells, it is only expressed at low levels, and increases as the cell nears terminal differentiation. 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 actin 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 myofibrils 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.
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 diaphragm and heart are affected. The mice without desmin are weaker and fatigue more easily than wild type mice   but the muscle fibers are less likely to be damaged during contraction  Mice without desmin also have impaired mitochondrial function.
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 filaments, instead forming aggregates of desmin and other proteins throughout the cell. Recently, mutations were identified in patients suffered by an arrhythmogenic right ventricular cardiomyopathy (ARVC).  Some of these DES mutations like p.N116S or p.E114del cause an aggregation of desmin within the cytoplasma.  Recently, a novel mutation p.A120D was discovered in family where several members had a sudden cardiac death.  It is also associated with Sarcoma botryoides (rhabdomyosarcoma variant) - a vaginal malignancy composed of spindle-shaped cells that affects girls < 4 years of age.
There are three major domains to this protein: a conserved alpha helix 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 domain 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.
- Muñoz-Mármol AM, Strasser G, Isamat M, Coulombe PA, Yang Y, Roca X, Vela E, Mate JL, Coll J, Fernández-Figueras MT, Navas-Palacios JJ, Ariza A, Fuchs E (September 1998). "A dysfunctional desmin mutation in a patient with severe generalized myopathy". Proc. Natl. Acad. Sci. U.S.A. 95 (19): 11312–7. doi:10.1073/pnas.95.19.11312. PMC 21639. PMID 9736733.
- Li ZL, Lilienbaum A, Butler-Browne G, Paulin D (May 1989). "Human desmin-coding gene: complete nucleotide sequence, characterization and regulation of expression during myogenesis and development". Gene 78 (2): 243–54. doi:10.1016/0378-1119(89)90227-8. PMID 2673923.
- The Human Protein Atlas. Proteinatlas.org. Retrieved on 2013-07-29.
- Lazarides E, Hubbard BD (December 1976). "Immunological characterization of the subunit of the 100 A filaments from muscle cells". Proc. Natl. Acad. Sci. U.S.A. 73 (12): 4344–8. doi:10.1073/pnas.73.12.4344. PMC 431448. PMID 1069986.
- Izant JG, Lazarides E (April 1977). "Invariance and heterogeneity in the major structural and regulatory proteins of chick muscle cells revealed by two-dimensional gel electrophoresis". Proc. Natl. Acad. Sci. U.S.A. 74 (4): 1450–4. doi:10.1073/pnas.74.4.1450. PMC 430794. PMID 266185.
- Costa ML, Escaleira R, Cataldo A, Oliveira F, Mermelstein CS (December 2004). "Desmin: molecular interactions and putative functions of the muscle intermediate filament protein". Braz. J. Med. Biol. Res. 37 (12): 1819–30. doi:10.1590/S0100-879X2004001200007. PMID 15558188.
- Bär H, Strelkov SV, Sjöberg G, Aebi U, Herrmann H (November 2004). "The biology of desmin filaments: how do mutations affect their structure, assembly, and organisation?". J. Struct. Biol. 148 (2): 137–52. doi:10.1016/j.jsb.2004.04.003. PMID 15477095.
- Li Z, Mericskay M, Agbulut O, Butler-Browne G, Carlsson L, Thornell LE, Babinet C, Paulin D (October 1997). "Desmin Is Essential for the Tensile Strength and Integrity of Myofibrils but Not for Myogenic Commitment, Differentiation, and Fusion of Skeletal Muscle". J. Cell Biol. 139 (1): 129–44. doi:10.1083/jcb.139.1.129. PMC 2139820. PMID 9314534.
- Stoeckert C (1997-03-16). "Dystrophin". Catalogue of Regulatory Elements. University of Pennsylvania. Retrieved 2010-06-28.
- Paulin D, Li Z (November 2004). "Desmin: a major intermediate filament protein essential for the structural integrity and function of muscle". Exp. Cell Res. 301 (1): 1–7. doi:10.1016/j.yexcr.2004.08.004. PMID 15501438.
- Shah SB, Davis J, Weisleder N, Kostavassili I, McCulloch AD, Ralston E, Capetanaki Y, Lieber RL (May 2004). "Structural and Functional Roles of Desmin in Mouse Skeletal Muscle during Passive Deformation". Biophys. J. 86 (5): 2993–3008. doi:10.1016/S0006-3495(04)74349-0. PMC 1304166. PMID 15111414.
- Goldfarb LG, Vicart P, Goebel HH, Dalakas MC (April 2004). "Desmin myopathy". Brain 127 (Pt 4): 723–34. doi:10.1093/brain/awh033. PMID 14724127.
- K Garcia-Pelagio, R Bloch, H Gonzáles-Serratos (2010). "Modeling the Cell Muscle Membrane from Normal and Desmin or Dystrophin null Mice as an Elastic System". AIP Conf. Proc. 1310 (1): 68–72.
- Sam M, Shah S, Fridén J, Milner DJ, Capetanaki Y, Lieber RL (October 2000). "Desmin knockout muscles generate lower stress and are less vulnerable to injury compared with wild-type muscles". Am. J. Physiol., Cell Physiol. 279 (4): C1116–22. PMID 11003592.
- Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Zu Knyphausen E, Vorgerd M, Gummert J, Milting H. De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy. Hum Mol Genet. 2010 Dec 1;19(23):4595-607. doi: 10.1093/hmg/ddq387. Epub 2010 Sep 9.
- Brodehl A, Hedde PN, Dieding M, Fatima A, Walhorn V, Gayda S, Šarić T, Klauke B, Gummert J, Anselmetti D, Heilemann M, Nienhaus GU, Milting H. Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants. J Biol Chem. 2012 May 4;287(19):16047-57. doi: 10.1074/jbc.M111.313841. Epub 2012 Mar 8. PMID: 22403400
- Brodehl A, Dieding M, Klauke B, Dec E, Madaan S, Huang T, Gargus J, Fatima A, Saric T, Cakar H, Walhorn V, Tönsing K, Skrzipczyk T, Cebulla R, Gerdes D, Schulz U, Gummert J, Svendsen JH, Olesen MS, Anselmetti D, Christensen AH, Kimonis V, Milting H.Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Zu Knyphausen E, Vorgerd M, Gummert J, Milting H. The novel desmin mutant p.A120D impairs filament formation, prevents intercalated disk localization, and causes sudden cardiac death. Circ Cardiovasc Genet. 2013 Dec;6(6):615-23. doi:10.1161/CIRCGENETICS.113.000103
- Meng JJ, Bornslaeger EA, Green KJ, Steinert PM, Ip W (August 1997). "Two-hybrid analysis reveals fundamental differences in direct interactions between desmoplakin and cell type-specific intermediate filaments". J. Biol. Chem. 272 (34): 21495–503. doi:10.1074/jbc.272.34.21495. PMID 9261168.
- GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy
- Desmin at the US National Library of Medicine Medical Subject Headings (MeSH)
- LOVD mutation database: DES