Skip to main content
SpringerLink
Log in
Book cover

The Cytoskeleton in Health and Disease pp 281–306Cite as

Desmin Filaments and Desmin-Related Myopathy

  • Chapter

  • 909 Accesses

Abstract

Desmin is the major intermediate filament protein in muscle tissue. In skeletal and cardiac muscle, desmin filaments distribute in the intermyofibrillar space to link adjacent myofibrils to each other at the z disc level, to the sarcolemma via costameres and sarcoglycan-dystroglycan complexes, and insert into to the nuclear envelope. The desmin filament network contributes to the positioning organelles such as mitochondria. In cardiac muscle, desmin is enriched in the intercalated disk by association with desmosomes. Hence, desmin plays an important role in the structural integrity and mechanical tension transmission across the myocyte and perhaps in the communication between cytoskeleton and extracellular matrix. Germ-line ablation of the desmin gene (DES) in mice does not affect muscle formation in embryos but causes postnatal cardiac and skeletal myopathies that deteriorate with age. A large number of mutations in DES or its partner proteins (e.g., CRYAB) cause desmin-related myopathy (DRM), a heterogeneous group of muscle disease featured by the presence of DES-positive aberrant protein aggregates in myocytes. Both disruption of the DES filament network as result of the mutation and gained toxicity of the mutant proteins may contribute to DRM pathogenesis but the precise pathogenesis remains poorly understood. Studies on DRM patients and DRM cell and animal models have also provided new insight into protein quality control in muscle tissue. Chemical chaperones, priming the proteasome, and enhancing autophagy have been shown to delay the progression of experimental DRM.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Lazarides E, Hubbard BD (1976) Immunological characterization of the subunit of the 100 A filaments from muscle cells. Proc Natl Acad Sci U S A 73:4344–4348

    PubMed Central  CAS  PubMed  Google Scholar 

  2. Goldfarb LG, Park KY, Cervenakova L, Gorokhova S, Lee HS, Vasconcelos O, Nagle JW, Semino-Mora C, Sivakumar K, Dalakas MC (1998) Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Nat Genet 19:402–403

    CAS  PubMed  Google Scholar 

  3. Munoz-Marmol AM, Strasser G, Isamat M, Coulombe PA, Yang Y, Roca X, Vela E, Mate JL, Coll J, Fernandez-Figueras MT, Navas-Palacios JJ, Ariza A, Fuchs E (1998) A dysfunctional desmin mutation in a patient with severe generalized myopathy. Proc Natl Acad Sci U S A 95:11312–11317

    PubMed Central  CAS  PubMed  Google Scholar 

  4. Vicart P, Caron A, Guicheney P, Li Z, Prevost MC, Faure A, Chateau D, Chapon F, Tome F, Dupret JM, Paulin D, Fardeau M (1998) A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet 20:92–95

    CAS  PubMed  Google Scholar 

  5. Capetanaki YG, Ngai J, Lazarides E (1984) Characterization and regulation in the expression of a gene coding for the intermediate filament protein desmin. Proc Natl Acad Sci U S A 81:6909–6913

    PubMed Central  CAS  PubMed  Google Scholar 

  6. Li ZL, Lilienbaum A, Butler-Browne G, Paulin D (1989) Human desmin-coding gene: complete nucleotide sequence, characterization and regulation of expression during myogenesis and development. Gene 78:243–254

    CAS  PubMed  Google Scholar 

  7. Viegas-Pequignot E, Li ZL, Dutrillaux B, Apiou F, Paulin D (1989) Assignment of human desmin gene to band 2q35 by nonradioactive in situ hybridization. Hum Genet 83:33–36

    CAS  PubMed  Google Scholar 

  8. Small JV, Sobieszek A (1977) Studies on the function and composition of the 10-NM(100-A) filaments of vertebrate smooth muscle. J Cell Sci 23:243–268

    CAS  PubMed  Google Scholar 

  9. Li ZL, Paulin D (1991) High level desmin expression depends on a muscle-specific enhancer. J Biol Chem 266:6562–6570

    CAS  PubMed  Google Scholar 

  10. Li Z, Paulin D (1993) Different factors interact with myoblast-specific and myotube-specific enhancer regions of the human desmin gene. J Biol Chem 268:10403–10415

    CAS  PubMed  Google Scholar 

  11. Li Z, Marchand P, Humbert J, Babinet C, Paulin D (1993) Desmin sequence elements regulating skeletal muscle-specific expression in transgenic mice. Development 117:947–959

    CAS  PubMed  Google Scholar 

  12. Li H, Capetanaki Y (1994) An E box in the desmin promoter cooperates with the E box and MEF-2 sites of a distal enhancer to direct muscle-specific transcription. EMBO J 13:3580–3589

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Kuisk IR, Li H, Tran D, Capetanaki Y (1996) A single MEF2 site governs desmin transcription in both heart and skeletal muscle during mouse embryogenesis. Dev Biol 174:1–13

    CAS  PubMed  Google Scholar 

  14. Schaart G, Viebahn C, Langmann W, Ramaekers F (1989) Desmin and titin expression in early postimplantation mouse embryos. Development 107:585–596

    CAS  PubMed  Google Scholar 

  15. Babai F, Musevi-Aghdam J, Schurch W, Royal A, Gabbiani G (1990) Coexpression of alpha-sarcomeric actin, alpha-smooth muscle actin and desmin during myogenesis in rat and mouse embryos I. Skeletal muscle. Differentiation 44:132–142

    CAS  PubMed  Google Scholar 

  16. Furst DO, Osborn M, Weber K (1989) Myogenesis in the mouse embryo: differential onset of expression of myogenic proteins and the involvement of titin in myofibril assembly. J Cell Biol 109:517–527

    CAS  PubMed  Google Scholar 

  17. Hill CS, Duran S, Lin ZX, Weber K, Holtzer H (1986) Titin and myosin, but not desmin, are linked during myofibrillogenesis in postmitotic mononucleated myoblasts. J Mol Biol 103:2185–2196

    CAS  Google Scholar 

  18. Brown JH, Cohen C, Parry DA (1996) Heptad breaks in alpha-helical coiled coils: stutters and stammers. Proteins 26:134–145

    CAS  PubMed  Google Scholar 

  19. Strelkov SV, Burkhard P (2002) Analysis of alpha-helical coiled coils with the program TWISTER reveals a structural mechanism for stutter compensation. J Struct Biol 137:54–64

    CAS  PubMed  Google Scholar 

  20. Herrmann H, Strelkov SV, Feja B, Rogers KR, Brettel M, Lustig A, Haner M, Parry DA, Steinert PM, Burkhard P, Aebi U (2000) The intermediate filament protein consensus motif of helix 2B: its atomic structure and contribution to assembly. J Mol Biol 298:817–832

    CAS  PubMed  Google Scholar 

  21. Herrmann H, Haner M, Brettel M, Muller SA, Goldie KN, Fedtke B, Lustig A, Franke WW, Aebi U (1996) Structure and assembly properties of the intermediate filament protein vimentin: the role of its head, rod and tail domains. J Mol Biol 264:933–953

    CAS  PubMed  Google Scholar 

  22. Heimburg T, Schuenemann J, Weber K, Geisler N (1996) Specific recognition of coiled coils by infrared spectroscopy: analysis of the three structural domains of type III intermediate filament proteins. Biochemistry 35:1375–1382

    CAS  PubMed  Google Scholar 

  23. Strelkov SV, Herrmann H, Geisler N, Wedig T, Zimbelmann R, Aebi U, Burkhard P (2002) Conserved segments 1A and 2B of the intermediate filament dimer: their atomic structures and role in filament assembly. EMBO J 21:1255–1266

    PubMed Central  CAS  PubMed  Google Scholar 

  24. Rogers KR, Eckelt A, Nimmrich V, Janssen KP, Schliwa M, Herrmann H, Franke WW (1995) Truncation mutagenesis of the non-alpha-helical carboxyterminal tail domain of vimentin reveals contributions to cellular localization but not to filament assembly. Eur J Cell Biol 66:136–150

    CAS  PubMed  Google Scholar 

  25. Lockard VG, Bloom S (1993) Trans-cellular desmin-lamin B intermediate filament network in cardiac myocytes. J Mol Cell Cardiol 25:303–309

    CAS  PubMed  Google Scholar 

  26. Konieczny P, Fuchs P, Reipert S, Kunz WS, Zeold A, Fischer I, Paulin D, Schroder R, Wiche G (2008) Myofiber integrity depends on desmin network targeting to Z-disks and costameres via distinct plectin isoforms. J Cell Biol 181:667–681

    PubMed Central  CAS  PubMed  Google Scholar 

  27. Poon E, Howman EV, Newey SE, Davies KE (2002) Association of syncoilin and desmin: linking intermediate filament proteins to the dystrophin-associated protein complex. J Biol Chem 277:3433–3439

    CAS  PubMed  Google Scholar 

  28. Kaplan SR, Gard JJ, Carvajal-Huerta L, Ruiz-Cabezas JC, Thiene G, Saffitz JE (2004) Structural and molecular pathology of the heart in Carvajal syndrome. Cardiovasc Pathol 13:26–32

    CAS  PubMed  Google Scholar 

  29. Bloom S, Lockard VG, Bloom M (1996) Intermediate filament-mediated stretch-induced changes in chromatin: a hypothesis for growth initiation in cardiac myocytes. J Mol Cell Cardiol 28:2123–2127

    CAS  PubMed  Google Scholar 

  30. Nikolova V, Leimena C, McMahon AC, Tan JC, Chandar S, Jogia D, Kesteven SH, Michalicek J, Otway R, Verheyen F, Rainer S, Stewart CL, Martin D, Feneley MP, Fatkin D (2004) Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C-deficient mice. J Clin Invest 113:357–369

    PubMed Central  CAS  PubMed  Google Scholar 

  31. McCullagh KJ, Edwards B, Poon E, Lovering RM, Paulin D, Davies KE (2007) Intermediate filament-like protein syncoilin in normal and myopathic striated muscle. Neuromuscul Disord 17:970–979

    PubMed  Google Scholar 

  32. Zhang J, Bang ML, Gokhin DS, Lu Y, Cui L, Li X, Gu Y, Dalton ND, Scimia MC, Peterson KL, Lieber RL, Chen J (2008) Syncoilin is required for generating maximum isometric stress in skeletal muscle but dispensable for muscle cytoarchitecture. Am J Physiol Cell Physiol 294:C1175–C1182

    PubMed Central  CAS  PubMed  Google Scholar 

  33. Li H, Choudhary SK, Milner DJ, Munir MI, Kuisk IR, Capetanaki Y (1994) Inhibition of desmin expression blocks myoblast fusion and interferes with the myogenic regulators MyoD and myogenin. J Cell Biol 124:827–841

    CAS  PubMed  Google Scholar 

  34. Weitzer G, Milner DJ, Kim JU, Bradley A, Capetanaki Y (1995) Cytoskeletal control of myogenesis: a desmin null mutation blocks the myogenic pathway during embryonic stem cell differentiation. Dev Biol 172:422–439

    CAS  PubMed  Google Scholar 

  35. Li Z, Colucci-Guyon E, Pincon-Raymond M, Mericskay M, Pournin S, Paulin D, Babinet C (1996) Cardiovascular lesions and skeletal myopathy in mice lacking desmin. Dev Biol 175:362–366

    CAS  PubMed  Google Scholar 

  36. Milner DJ, Weitzer G, Tran D, Bradley A, Capetanaki Y (1996) Disruption of muscle architecture and myocardial degeneration in mice lacking desmin. J Cell Biol 134:1255–1270

    CAS  PubMed  Google Scholar 

  37. Li Z, Mericskay M, Agbulut O, Butler-Browne G, Carlsson L, Thornell LE, Babinet C, Paulin D (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 139:129–144

    PubMed Central  CAS  PubMed  Google Scholar 

  38. Milner DJ, Taffet GE, Wang X, Pham T, Tamura T, Hartley C, Gerdes AM, Capetanaki Y (1999) The absence of desmin leads to cardiomyocyte hypertrophy and cardiac dilation with compromised systolic function. J Mol Cell Cardiol 31:2063–2076

    CAS  PubMed  Google Scholar 

  39. Thornell L, Carlsson L, Li Z, Mericskay M, Paulin D (1997) Null mutation in the desmin gene gives rise to a cardiomyopathy. J Mol Cell Cardiol 29:2107–2124

    CAS  PubMed  Google Scholar 

  40. Capetanaki Y, Milner DJ, Weitzer G (1997) Desmin in muscle formation and maintenance: knockouts and consequences. Cell Struct Funct 22:103–116

    CAS  PubMed  Google Scholar 

  41. Weisleder N, Soumaka E, Abbasi S, Taegtmeyer H, Capetanaki Y (2004) Cardiomyocyte-specific desmin rescue of desmin null cardiomyopathy excludes vascular involvement. J Mol Cell Cardiol 36:121–128

    CAS  PubMed  Google Scholar 

  42. Wede OK, Lofgren M, Li Z, Paulin D, Arner A (2002) Mechanical function of intermediate filaments in arteries of different size examined using desmin deficient mice. J Physiol 540:941–949

    PubMed Central  CAS  PubMed  Google Scholar 

  43. Milner DJ, Mavroidis M, Weisleder N, Capetanaki Y (2000) Desmin cytoskeleton linked to muscle mitochondrial distribution and respiratory function. J Cell Biol 150:1283–1298

    PubMed Central  CAS  PubMed  Google Scholar 

  44. Weisleder N, Taffet GE, Capetanaki Y (2004) Bcl-2 overexpression corrects mitochondrial defects and ameliorates inherited desmin null cardiomyopathy. Proc Natl Acad Sci U S A 101:769–774

    PubMed Central  CAS  PubMed  Google Scholar 

  45. Slats AM, Janssen K, van Schadewijk A, van der Plas DT, Schot R, van den Aardweg JG, de Jongste JC, Hiemstra PS, Mauad T, Rabe KF, Sterk PJ (2008) Expression of smooth muscle and extracellular matrix proteins in relation to airway function in asthma. J Allergy Clin Immunol 121:1196–1202

    CAS  PubMed  Google Scholar 

  46. Shardonofsky FR, Capetanaki Y, Boriek AM (2006) Desmin modulates lung elastic recoil and airway responsiveness. Am J Physiol Lung Cell Mol Physiol 290:L890–L896

    CAS  PubMed  Google Scholar 

  47. Mohamed JS, Hajira A, Li Z, Paulin D, Boriek AM (2011) Desmin regulates airway smooth muscle hypertrophy through early growth-responsive protein-1 and microRNA-26a. J Biol Chem 286:43394–43404

    PubMed Central  CAS  PubMed  Google Scholar 

  48. Scott RS, Li Z, Paulin D, Uvelius B, Small JV, Arner A (2008) Role of desmin in active force transmission and maintenance of structure during growth of urinary bladder. Am J Physiol Cell Physiol 295:C324–C331

    CAS  PubMed  Google Scholar 

  49. Lazarides E (1980) Intermediate filaments as mechanical integrators of cellular space. Nature 283:249–256

    CAS  PubMed  Google Scholar 

  50. Fichna JP, Karolczak J, Potulska-Chromik A, Miszta P, Berdynski M, Sikorska A, Filipek S, Redowicz MJ, Kaminska A, Zekanowski C (2014) Two desmin gene mutations associated with myofibrillar myopathies in polish families. PLoS One 9:e115470

    PubMed Central  PubMed  Google Scholar 

  51. Schroder R, Schoser B (2009) Myofibrillar myopathies: a clinical and myopathological guide. Brain Pathol 19:483–492

    PubMed  Google Scholar 

  52. Goldfarb LG, Dalakas MC (2009) Tragedy in a heartbeat: malfunctioning desmin causes skeletal and cardiac muscle disease. J Clin Invest 119:1806–1813

    PubMed Central  CAS  PubMed  Google Scholar 

  53. Park KY, Dalakas MC, Goebel HH, Ferrans VJ, Semino-Mora C, Litvak S, Takeda K, Goldfarb LG (2000) Desmin splice variants causing cardiac and skeletal myopathy. J Med Genet 37:851–857

    PubMed Central  CAS  PubMed  Google Scholar 

  54. Iwaki T, Kume-Iwaki A, Liem RK, Goldman JE (1989) Alpha B-crystallin is expressed in non-lenticular tissues and accumulates in Alexander’s disease brain. Cell 57:71–78

    CAS  PubMed  Google Scholar 

  55. Sacconi S, Feasson L, Antoine JC, Pecheux C, Bernard R, Cobo AM, Casarin A, Salviati L, Desnuelle C, Urtizberea A (2012) A novel CRYAB mutation resulting in multisystemic disease. Neuromuscul Disord 22:66–72

    PubMed  Google Scholar 

  56. Reilich P, Schoser B, Schramm N, Krause S, Schessl J, Kress W, Muller-Hocker J, Walter MC, Lochmuller H (2010) The p.G154S mutation of the alpha-B crystallin gene (CRYAB) causes late-onset distal myopathy. Neuromuscul Disord 20:255–259

    PubMed  Google Scholar 

  57. Inagaki N, Hayashi T, Arimura T, Koga Y, Takahashi M, Shibata H, Teraoka K, Chikamori T, Yamashina A, Kimura A (2006) Alpha B-crystallin mutation in dilated cardiomyopathy. Biochem Biophys Res Commun 342:379–386

    CAS  PubMed  Google Scholar 

  58. Selcen D, Engel AG (2003) Myofibrillar myopathy caused by novel dominant negative alpha B-crystallin mutations. Ann Neurol 54:804–810

    CAS  PubMed  Google Scholar 

  59. Del Bigio MR, Chudley AE, Sarnat HB, Campbell C, Goobie S, Chodirker BN, Selcen D (2011) Infantile muscular dystrophy in Canadian aboriginals is an alphaB-crystallinopathy. Ann Neurol 69:866–871

    PubMed Central  PubMed  Google Scholar 

  60. Forrest KM, Al-Sarraj S, Sewry C, Buk S, Tan SV, Pitt M, Durward A, McDougall M, Irving M, Hanna MG, Matthews E, Sarkozy A, Hudson J, Barresi R, Bushby K, Jungbluth H, Wraige E (2011) Infantile onset myofibrillar myopathy due to recessive CRYAB mutations. Neuromuscul Disord 21:37–40

    PubMed  Google Scholar 

  61. Berry V, Francis P, Reddy MA, Collyer D, Vithana E, MacKay I, Dawson G, Carey AH, Moore A, Bhattacharya SS, Quinlan RA (2001) Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans. Am J Hum Genet 69:1141–1145

    PubMed Central  CAS  PubMed  Google Scholar 

  62. Liu M, Ke T, Wang Z, Yang Q, Chang W, Jiang F, Tang Z, Li H, Ren X, Wang X, Wang T, Li Q, Yang J, Liu J, Wang QK (2006) Identification of a CRYAB mutation associated with autosomal dominant posterior polar cataract in a Chinese family. Invest Ophthalmol Vis Sci 47:3461–3466

    PubMed  Google Scholar 

  63. Xia XY, Wu QY, An LM, Li WW, Li N, Li TF, Zhang C, Cui YX, Li XJ, Xue CY (2014) A novel P20R mutation in the alpha-B crystallin gene causes autosomal dominant congenital posterior polar cataracts in a Chinese family. BMC Ophthalmol 14:108

    PubMed Central  PubMed  Google Scholar 

  64. Devi RR, Yao W, Vijayalakshmi P, Sergeev YV, Sundaresan P, Hejtmancik JF (2008) Crystallin gene mutations in Indian families with inherited pediatric cataract. Mol Vis 14:1157–1170

    PubMed Central  CAS  PubMed  Google Scholar 

  65. Selcen D, Muntoni F, Burton BK, Pegoraro E, Sewry C, Bite AV, Engel AG (2009) Mutation in BAG3 causes severe dominant childhood muscular dystrophy. Ann Neurol 65:83–89

    PubMed Central  CAS  PubMed  Google Scholar 

  66. Wang X, Osinska H, Dorn GW 2nd, Nieman M, Lorenz JN, Gerdes AM, Witt S, Kimball T, Gulick J, Robbins J (2001) Mouse model of desmin-related cardiomyopathy. Circulation 103:2402–2407

    CAS  PubMed  Google Scholar 

  67. Kostareva A, Sjoberg G, Bruton J, Zhang SJ, Balogh J, Gudkova A, Hedberg B, Edstrom L, Westerblad H, Sejersen T (2008) Mice expressing L345P mutant desmin exhibit morphological and functional changes of skeletal and cardiac mitochondria. J Muscle Res Cell Motil 29:25–36

    CAS  PubMed  Google Scholar 

  68. Mavroidis M, Panagopoulou P, Kostavasili I, Weisleder N, Capetanaki Y (2008) A missense mutation in desmin tail domain linked to human dilated cardiomyopathy promotes cleavage of the head domain and abolishes its Z-disc localization. FASEB J 22:3318–3327

    PubMed Central  CAS  PubMed  Google Scholar 

  69. Clemen CS, Stockigt F, Strucksberg KH, Chevessier F, Winter L, Schutz J, Bauer R, Thorweihe JM, Wenzel D, Schlotzer-Schrehardt U, Rasche V, Krsmanovic P, Katus HA, Rottbauer W, Just S, Muller OJ, Friedrich O, Meyer R, Herrmann H, Schrickel JW, Schroder R (2015) The toxic effect of R350P mutant desmin in striated muscle of man and mouse. Acta Neuropathol 129:297–315

    PubMed Central  CAS  PubMed  Google Scholar 

  70. Wang X, Osinska H, Klevitsky R, Gerdes AM, Nieman M, Lorenz J, Hewett T, Robbins J (2001) Expression of R120G-alphaB-crystallin causes aberrant desmin and alphaB-crystallin aggregation and cardiomyopathy in mice. Circ Res 89:84–91

    CAS  PubMed  Google Scholar 

  71. Rajasekaran NS, Connell P, Christians ES, Yan LJ, Taylor RP, Orosz A, Zhang XQ, Stevenson TJ, Peshock RM, Leopold JA, Barry WH, Loscalzo J, Odelberg SJ, Benjamin IJ (2007) Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell 130:427–439

    PubMed Central  CAS  PubMed  Google Scholar 

  72. Andley UP, Hamilton PD, Ravi N, Weihl CC (2011) A knock-in mouse model for the R120G mutation of alphaB-crystallin recapitulates human hereditary myopathy and cataracts. PLoS One 6:e17671

    PubMed Central  CAS  PubMed  Google Scholar 

  73. Bar H, Mucke N, Kostareva A, Sjoberg G, Aebi U, Herrmann H (2005) Severe muscle disease-causing desmin mutations interfere with in vitro filament assembly at distinct stages. Proc Natl Acad Sci U S A 102:15099–15104

    PubMed Central  PubMed  Google Scholar 

  74. Winter DL, Paulin D, Mericskay M, Li Z (2014) Posttranslational modifications of desmin and their implication in biological processes and pathologies. Histochem Cell Biol 141:1–16

    CAS  PubMed  Google Scholar 

  75. Cohen S, Zhai B, Gygi SP, Goldberg AL (2012) Ubiquitylation by Trim32 causes coupled loss of desmin, Z-bands, and thin filaments in muscle atrophy. J Cell Biol 198:575–589

    PubMed Central  CAS  PubMed  Google Scholar 

  76. Caron A, Chapon F (1999) Desmin phosphorylation abnormalities in cytoplasmic body and desmin-related myopathies. Muscle Nerve 22:1122–1125

    CAS  PubMed  Google Scholar 

  77. Janue A, Odena MA, Oliveira E, Olive M, Ferrer I (2007) Desmin is oxidized and nitrated in affected muscles in myotilinopathies and desminopathies. J Neuropathol Exp Neurol 66:711–723

    CAS  PubMed  Google Scholar 

  78. Li D, Tapscoft T, Gonzalez O, Burch PE, Quinones MA, Zoghbi WA, Hill R, Bachinski LL, Mann DL, Roberts R (1999) Desmin mutation responsible for idiopathic dilated cardiomyopathy. Circulation 100:461–464

    CAS  PubMed  Google Scholar 

  79. Maloyan A, Sanbe A, Osinska H, Westfall M, Robinson D, Imahashi K, Murphy E, Robbins J (2005) Mitochondrial dysfunction and apoptosis underlie the pathogenic process in alpha-B-crystallin desmin-related cardiomyopathy. Circulation 112:3451–3461

    PubMed Central  CAS  PubMed  Google Scholar 

  80. Maloyan A, Osinska H, Lammerding J, Lee RT, Cingolani OH, Kass DA, Lorenz JN, Robbins J (2009) Biochemical and mechanical dysfunction in a mouse model of desmin-related myopathy. Circ Res 104:1021–1028

    PubMed Central  CAS  PubMed  Google Scholar 

  81. Wang X, Robbins J (2006) Heart failure and protein quality control. Circ Res 99:1315–1328

    CAS  PubMed  Google Scholar 

  82. Wang X, Pattison JS, Su H (2013) Posttranslational modification and quality control. Circ Res 112:367–381

    PubMed Central  CAS  PubMed  Google Scholar 

  83. Wang X, Klevitsky R, Huang W, Glasford J, Li F, Robbins J (2003) AlphaB-crystallin modulates protein aggregation of abnormal desmin. Circ Res 93:998–1005

    CAS  PubMed  Google Scholar 

  84. Bova MP, Yaron O, Huang Q, Ding L, Haley DA, Stewart PL, Horwitz J (1999) Mutation R120G in alphaB-crystallin, which is linked to a desmin-related myopathy, results in an irregular structure and defective chaperone-like function. Proc Natl Acad Sci U S A 96:6137–6142

    PubMed Central  CAS  PubMed  Google Scholar 

  85. Perng MD, Muchowski PJ, van Den IP, Wu GJ, Hutcheson AM, Clark JI, Quinlan RA (1999) The cardiomyopathy and lens cataract mutation in alphaB-crystallin alters its protein structure, chaperone activity, and interaction with intermediate filaments in vitro. J Biol Chem 274:33235–33243

    CAS  PubMed  Google Scholar 

  86. Chen Q, Liu JB, Horak KM, Zheng H, Kumarapeli AR, Li J, Li F, Gerdes AM, Wawrousek EF, Wang X (2005) Intrasarcoplasmic amyloidosis impairs proteolytic function of proteasomes in cardiomyocytes by compromising substrate uptake. Circ Res 97:1018–1026

    CAS  PubMed  Google Scholar 

  87. Liu J, Chen Q, Huang W, Horak KM, Zheng H, Mestril R, Wang X (2006) Impairment of the ubiquitin-proteasome system in desminopathy mouse hearts. FASEB J 20:362–364

    CAS  PubMed  Google Scholar 

  88. Kumarapeli AR, Horak KM, Glasford JW, Li J, Chen Q, Liu J, Zheng H, Wang X (2005) A novel transgenic mouse model reveals deregulation of the ubiquitin-proteasome system in the heart by doxorubicin. FASEB J 19:2051–2053

    PubMed  Google Scholar 

  89. Bence NF, Sampat RM, Kopito RR (2001) Impairment of the ubiquitin-proteasome system by protein aggregation. Science 292:1552–1555

    CAS  PubMed  Google Scholar 

  90. Liu J, Tang M, Mestril R, Wang X (2006) Aberrant protein aggregation is essential for a mutant desmin to impair the proteolytic function of the ubiquitin-proteasome system in cardiomyocytes. J Mol Cell Cardiol 40:451–454

    CAS  PubMed  Google Scholar 

  91. Li J, Horak KM, Su H, Sanbe A, Robbins J, Wang X (2011) Enhancement of proteasomal function protects against cardiac proteinopathy and ischemia/reperfusion injury in mice. J Clin Invest 121:3689–3700

    PubMed Central  CAS  PubMed  Google Scholar 

  92. Ranek MJ, Terpstra EJ, Li J, Kass DA, Wang X (2013) Protein kinase g positively regulates proteasome-mediated degradation of misfolded proteins. Circulation 128:365–376

    PubMed Central  CAS  PubMed  Google Scholar 

  93. Weihl CC, Iyadurai S, Baloh RH, Pittman SK, Schmidt RE, Lopate G, Pestronk A, Harms MB (2015) Autophagic vacuolar pathology in desminopathies. Neuromuscul Disord 25:199–206

    PubMed  Google Scholar 

  94. Tannous P, Zhu H, Johnstone JL, Shelton JM, Rajasekaran NS, Benjamin IJ, Nguyen L, Gerard RD, Levine B, Rothermel BA, Hill JA (2008) Autophagy is an adaptive response in desmin-related cardiomyopathy. Proc Natl Acad Sci U S A 105:9745–9750

    PubMed Central  CAS  PubMed  Google Scholar 

  95. Zheng Q, Su H, Ranek MJ, Wang X (2011) Autophagy and p62 in cardiac proteinopathy. Circ Res 109:296–308

    PubMed Central  CAS  PubMed  Google Scholar 

  96. Bhuiyan MS, Pattison JS, Osinska H, James J, Gulick J, McLendon PM, Hill JA, Sadoshima J, Robbins J (2013) Enhanced autophagy ameliorates cardiac proteinopathy. J Clin Invest 123:5284–5297

    PubMed Central  CAS  PubMed  Google Scholar 

  97. Pattison JS, Osinska H, Robbins J (2011) Atg7 induces basal autophagy and rescues autophagic deficiency in CryABR120G cardiomyocytes. Circ Res 109:151–160

    PubMed Central  CAS  PubMed  Google Scholar 

  98. Kannan S, Muthusamy VR, Whitehead KJ, Wang L, Gomes AV, Litwin SE, Kensler TW, Abel ED, Hoidal JR, Rajasekaran NS (2013) Nrf2 deficiency prevents reductive stress-induced hypertrophic cardiomyopathy. Cardiovasc Res 100:63–73

    PubMed Central  CAS  PubMed  Google Scholar 

  99. Rajasekaran NS, Varadharaj S, Khanderao GD, Davidson CJ, Kannan S, Firpo MA, Zweier JL, Benjamin IJ (2011) Sustained activation of nuclear erythroid 2-related factor 2/antioxidant response element signaling promotes reductive stress in the human mutant protein aggregation cardiomyopathy in mice. Antioxid Redox Signal 14:957–971

    PubMed Central  CAS  PubMed  Google Scholar 

  100. Maloyan A, Gulick J, Glabe CG, Kayed R, Robbins J (2007) Exercise reverses preamyloid oligomer and prolongs survival in alphaB-crystallin-based desmin-related cardiomyopathy. Proc Natl Acad Sci U S A 104:5995–6000

    PubMed Central  CAS  PubMed  Google Scholar 

  101. Sanbe A, Osinska H, Saffitz JE, Glabe CG, Kayed R, Maloyan A, Robbins J (2004) Desmin-related cardiomyopathy in transgenic mice: a cardiac amyloidosis. Proc Natl Acad Sci U S A 101:10132–10136

    PubMed Central  CAS  PubMed  Google Scholar 

  102. Zheng H, Tang M, Zheng Q, Kumarapeli AR, Horak KM, Tian Z, Wang X (2010) Doxycycline attenuates protein aggregation in cardiomyocytes and improves survival of a mouse model of cardiac proteinopathy. J Am Coll Cardiol 56:1418–1426

    PubMed Central  CAS  PubMed  Google Scholar 

  103. Zhang H, Wang X (2015) Priming the proteasome by protein kinase G: a novel cardioprotective mechanism of sildenafil. Future Cardiol 11:177–189

    CAS  PubMed  Google Scholar 

  104. McLendon PM, Ferguson BS, Osinska H, Bhuiyan MS, James J, McKinsey TA, Robbins J (2014) Tubulin hyperacetylation is adaptive in cardiac proteotoxicity by promoting autophagy. Proc Natl Acad Sci U S A 111:E5178–E5186

    PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Basic Biomedical Sciences, Sanford School of Medicine of the University of South Dakota, 414 East Clark Street, Lee Medical Sciences Building, Vermillion, SD, 57069, USA

    Xuejun Wang

Authors
  1. Xuejun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xuejun Wang .

Editor information

Editors and Affiliations

  1. Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, Missouri, USA

    Heide Schatten

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Wang, X. (2015). Desmin Filaments and Desmin-Related Myopathy. In: Schatten, H. (eds) The Cytoskeleton in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2904-7_12

Download citation

Publish with us

Policies and ethics

Search

Navigation