Open Access Articles- Top Results for Desmin


SymbolsDES ; CSM1; CSM2; LGMD2R
External IDsOMIM125660 MGI94885 HomoloGene56469 GeneCards: DES Gene
RNA expression pattern
File:PBB GE DES 202222 s at tn.png
File:PBB GE DES 214027 x at tn.png
More reference expression data
RefSeq (mRNA)NM_001927NM_010043
RefSeq (protein)NP_001918NP_034173
Location (UCSC)Chr 2:
220.28 – 220.29 Mb
Chr 1:
75.36 – 75.37 Mb
PubMed search[1][2]

Desmin is a protein that in humans is encoded by the DES gene.[1][2] Desmin is a muscle-specific, type III[3] intermediate filament that integrates the sarcolemma, Z disk and nuclear membrane in sarcomeres and regulates sarcomere architecture.[4]


Desmin is a 53.5 kD protein composed of 470 amino acids.[5][6] There are three major domains to the desmin protein: a conserved alpha helix rod, a variable non alpha helix head, and a carboxy-terminal tail.[7] Desmin, as all intermediate filaments, shows no polarity when assembled.[7] The rod domain consists of 308 amino acids with parallel alpha helical coiled coil dimers and three linkers to disrupt it.[7] 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.[7] The tail domain is responsible for the integration of filaments and interaction with proteins and organelles. Desmin is only expressed in vertebrates, however homologous proteins are found in many organisms.[7] Desmin is a subunit of intermediate filaments in cardiac muscle, skeletal muscle and smooth muscle tissue.[8] In cardiac muscle, desmin is present in Z-discs and intercalated discs. Desmin has been shown to interact with desmoplakin[9] and αB-crystallin.[10]


Desmin was first described in 1976,[11] first purified in 1977,[12] the gene was cloned in 1989,[2] and the first knockout mouse was created in 1996.[13] The function of desmin has been deduced through studies in knockout mice. Desmin is one of the earliest protein markers for muscle tissue in embryogenesis as it is detected in the somites.[7] 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.[8] 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.[14]

In adult desmin-null mice, hearts from 10 wk-old animals showed drastic alterations in muscle architecture, including a misalignment of myofibrils and disorganization and swelling of mitochondria; findings that were more severe in cardiac relative to skeletal muscle. Cardiac tissue also exhibited progressive necrosis and calcification of the myocardium.[15] A separate study examined this in more detail in cardiac tissue and found that murine hearts lacking desmin developed hypertrophic cardiomyopathy and chamber dilation combined with systolic dysfunction.[16] In adult muscle, desmin forms a scaffold around the Z-disk of the sarcomere and connects the Z-disk to the subsarcolemmal cytoskeleton.[17] It links the myofibrils laterally by connecting the Z-disks.[7] Through its connection to the sarcomere, desmin connects the contractile apparatus to the cell nucleus, mitochondria, and post-synaptic areas of motor endplates.[7] These connections maintain the structural and mechanical integrity of the cell during contraction while also helping in force transmission and longitudinal load bearing.[17][18] In human heart failure, desmin expression is upregulated, which has been hyopthesized to be a defense mechanism in an attempt to maintain normal sarcomere alignment amidst disease pathogenesis.[19] 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.[18] Finally, desmin may be important in mitochondria function. When desmin is not functioning properly there is improper mitochondrial distribution, number, morphology and function.[20][21] 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.

Clinical significance

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, and rather, forms aggregates of desmin and other proteins throughout the cell.[7] Desmin mutations have been associated with restrictive and idopathic cardiomyopathy.;[22][23] and recently, mutations were identified in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC).[24][25] Some of these DES mutations like p.N116S or p.E114del cause an aggregation of desmin within the cytoplasm.[26] A mutation p.A120D was discovered in a family where several members had sudden cardiac death.[27]


  1. Muñoz-Mármol AM, Strasser G, Isamat M, Coulombe PA, Yang Y, Roca X et al. (September 1998). "A dysfunctional desmin mutation in a patient with severe generalized myopathy". Proc. Natl. Acad. Sci. U.S.A. 95 (19): 11312–7. PMC 21639. PMID 9736733. doi:10.1073/pnas.95.19.11312. 
  2. 2.0 2.1 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. PMID 2673923. doi:10.1016/0378-1119(89)90227-8. 
  3. The Human Protein Atlas. Retrieved on 2013-07-29.
  4. Sequeira V, Nijenkamp LL, Regan JA, van der Velden J (Feb 2014). "The physiological role of cardiac cytoskeleton and its alterations in heart failure". Biochimica Et Biophysica Acta 1838 (2). PMID 23860255. doi:10.1016/j.bbamem.2013.07.011. 
  5.  Missing or empty |title= (help)
  6. Zong, N. C.; Li, H; Li, H; Lam, M. P.; Jimenez, R. C.; Kim, C. S.; Deng, N; Kim, A. K.; Choi, J. H.; Zelaya, I; Liem, D; Meyer, D; Odeberg, J; Fang, C; Lu, H. J.; Xu, T; Weiss, J; Duan, H; Uhlen, M; Yates Jr, 3rd; Apweiler, R; Ge, J; Hermjakob, H; Ping, P (2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. PMC 4076475. PMID 23965338. doi:10.1161/CIRCRESAHA.113.301151.  edit
  7. 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 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. PMID 15477095. doi:10.1016/j.jsb.2004.04.003. 
  8. 8.0 8.1 Li Z, Mericskay M, Agbulut O, Butler-Browne G, Carlsson L, Thornell LE et al. (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. PMC 2139820. PMID 9314534. doi:10.1083/jcb.139.1.129. 
  9. 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. PMID 9261168. doi:10.1074/jbc.272.34.21495. 
  10. Bennardini, F; Wrzosek, A; Chiesi, M (1992). "Alpha B-crystallin in cardiac tissue. Association with actin and desmin filaments". Circulation research 71 (2): 288–94. PMID 1628387.  edit
  11. 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. PMC 431448. PMID 1069986. doi:10.1073/pnas.73.12.4344. 
  12. 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. PMC 430794. PMID 266185. doi:10.1073/pnas.74.4.1450. 
  13. 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. PMID 15558188. doi:10.1590/S0100-879X2004001200007. 
  14. Stoeckert C (1997-03-16). "Dystrophin". Catalogue of Regulatory Elements. University of Pennsylvania. Retrieved 2010-06-28. 
  15. Milner DJ, Weitzer G, Tran D, Bradley A, Capetanaki Y (Sep 1996). "Disruption of muscle architecture and myocardial degeneration in mice lacking desmin". The Journal of Cell Biology 134 (5). PMID 8794866. 
  16. Milner DJ, Taffet GE, Wang X, Pham T, Tamura T, Hartley C et al. (Nov 1999). "The absence of desmin leads to cardiomyocyte hypertrophy and cardiac dilation with compromised systolic function". Journal of Molecular and Cellular Cardiology 31 (11). PMID 10591032. 
  17. 17.0 17.1 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. PMID 15501438. doi:10.1016/j.yexcr.2004.08.004. 
  18. 18.0 18.1 Shah SB, Davis J, Weisleder N, Kostavassili I, McCulloch AD, Ralston E et al. (May 2004). "Structural and functional roles of desmin in mouse skeletal muscle during passive deformation". Biophys. J. 86 (5): 2993–3008. PMC 1304166. PMID 15111414. doi:10.1016/S0006-3495(04)74349-0. 
  19. Heling A, Zimmermann R, Kostin S, Maeno Y, Hein S, Devaux B et al. (Apr 2000). "Increased expression of cytoskeletal, linkage, and extracellular proteins in failing human myocardium". Circulation Research 86 (8). PMID 10785506. 
  20. Milner DJ, Mavroidis M, Weisleder N, Capetanaki Y (2000). "Desmin cytoskeleton linked to muscle mitochondrial distribution and respiratory function.". Journal of Cell Biology 150: 1283–1298. doi:10.1083/jcb.150.6.1283. 
  21. Goldfarb LG, Vicart P, Goebel HH, Dalakas MC (April 2004). "Desmin myopathy". Brain 127 (Pt 4): 723–34. PMID 14724127. doi:10.1093/brain/awh033. 
  22. Li D, Tapscoft T, Gonzalez O, Burch PE, Quiñones MA, Zoghbi WA et al. (Aug 1999). "Desmin mutation responsible for idiopathic dilated cardiomyopathy". Circulation 100 (5). PMID 10430757. 
  23. Goldfarb LG, Park KY, Cervenáková L, Gorokhova S, Lee HS, Vasconcelos O et al. (Aug 1998). "Missense mutations in desmin associated with familial cardiac and skeletal myopathy". Nature Genetics 19 (4). PMID 9697706. doi:10.1038/1300. 
  24. Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A et al. (2010). "De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy". Hum. Mol. Genet. 19 (23): 4595–607. PMID 20829228. doi:10.1093/hmg/ddq387. 
  25. Lorenzon A, Beffagna G, Bauce B, De Bortoli M, Li Mura IE, Calore M et al. (Feb 2013). "Desmin mutations and arrhythmogenic right ventricular cardiomyopathy". The American Journal of Cardiology 111 (3). PMID 23168288. doi:10.1016/j.amjcard.2012.10.017. 
  26. Brodehl A, Hedde PN, Dieding M, Fatima A, Walhorn V, Gayda S et al. (2012). "Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants". J. Biol. Chem. 287 (19): 16047–57. PMC 3346104. PMID 22403400. doi:10.1074/jbc.M111.313841. 
  27. Brodehl A, Dieding M, Klauke B, Dec E, Madaan S, Huang T et al. (2013). "The novel desmin mutant p.A120D impairs filament formation, prevents intercalated disk localization, and causes sudden cardiac death". Circ Cardiovasc Genet 6 (6): 615–23. PMID 24200904. doi:10.1161/CIRCGENETICS.113.000103. 

External links

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