Acta Neuropathologica

, Volume 125, Issue 1, pp 77–93 | Cite as

The many faces of plectin and plectinopathies: pathology and mechanisms

  • Lilli Winter
  • Gerhard WicheEmail author


Plectin, a giant multifunctional cytolinker protein, plays a crucial role in stabilizing and orchestrating intermediate filament networks in cells. Mutations in the human plectin gene result in multiple diseases manifesting with muscular dystrophy, skin blistering, and signs of neuropathy. The most common disease caused by plectin deficiency is epidermolysis bullosa simplex (EBS)-MD, a rare autosomal-recessive skin blistering disorder with late-onset muscular dystrophy. EBS-MD patients and plectin-deficient mice display pathologic desmin-positive protein aggregates, degenerated myofibrils, and mitochondrial abnormalities, the hallmarks of myofibrillar myopathies. In addition to EBS-MD, plectin mutations have been shown to cause EBS-MD with a myasthenic syndrome, limb-girdle muscular dystrophy type 2Q, EBS with pyloric atresia, and EBS-Ogna. This review focuses on clinical and pathological manifestations of these plectinopathies. It addresses especially plectin’s role in skeletal muscle, where a loss of muscle fiber integrity and profound changes of myofiber cytoarchitecture are observed in its absence. Furthermore, the highly complex genetic and molecular structure of plectin is discussed; a high number of differentially spliced exons give rise to a variety of different isoforms, which fulfill distinct functions in different cell types and tissues. Plectin’s abilities to act as a dynamic organizer of intermediate filament networks and to interact with a multitude of different interaction partners are the basis for its function as a scaffolding platform for proteins involved in signaling. Finally, the article addresses a series of genetically manipulated mouse lines that were generated to serve as powerful models to study functional and molecular consequences of plectin gene defects.


Plectin Cytolinker proteins Intermediate filaments Epidermolysis bullosa simplex Muscular dystrophy 



The work described from the authors’ laboratory was supported by the Austrian Science Research Grants P23729-B11 and I413-B09 (part of the Multilocation DFG-Research Unit 1228 “Molecular Pathogenesis of Myofibrillar Myopathies”).


  1. 1.
    Abrahamsberg C, Fuchs P, Osmanagic-Myers S, Fischer I, Propst F, Elbe-Bürger A, Wiche G (2005) Targeted ablation of plectin isoform 1 uncovers role of cytolinker proteins in leukocyte recruitment. Proc Natl Acad Sci USA 102(51):18449–18454PubMedCrossRefGoogle Scholar
  2. 2.
    Ackerl R, Walko G, Fuchs P, Fischer I, Schmuth M, Wiche G (2007) Conditional targeting of plectin in prenatal and adult mouse stratified epithelia causes keratinocyte fragility and lesional epidermal barrier defects. J Cell Sci 120(Pt 14):2435–2443PubMedCrossRefGoogle Scholar
  3. 3.
    Andrä K, Lassmann H, Bittner R, Shorny S, Fässler R, Propst F, Wiche G (1997) Targeted inactivation of plectin reveals essential function in maintaining the integrity of skin, muscle, and heart cytoarchitecture. Genes Dev 11(23):3143–3156PubMedCrossRefGoogle Scholar
  4. 4.
    Andrä K, Nikolic B, Stöcher M, Drenckhahn D, Wiche G (1998) Not just scaffolding: plectin regulates actin dynamics in cultured cells. Genes Dev 12(21):3442–3451PubMedCrossRefGoogle Scholar
  5. 5.
    Baker KE, Condon C (2004) Under the Tucson sun: a meeting in the desert on mRNA decay. RNA 10(11):1680–1691PubMedCrossRefGoogle Scholar
  6. 6.
    Banwell BL, Russel J, Fukudome T, Shen XM, Stilling G, Engel AG (1999) Myopathy, myasthenic syndrome, and epidermolysis bullosa simplex due to plectin deficiency. J Neuropathol Exp Neurol 58(8):832–846PubMedCrossRefGoogle Scholar
  7. 7.
    Bauer JW, Rouan F, Kofler B, Rezniczek GA, Kornacker I, Muss W, Hametner R, Klausegger A, Huber A, Pohla-Gubo G, Wiche G, Uitto J, Hintner H (2001) A compound heterozygous one amino-acid insertion/nonsense mutation in the plectin gene causes epidermolysis bullosa simplex with plectin deficiency. Am J Pathol 158(2):617–625. pii:S0002-9440(10)64003-5Google Scholar
  8. 8.
    Bausch D, Mino-Kenudson M, Fernandez-Del Castillo C, Warshaw AL, Kelly KA, Thayer SP (2009) Plectin-1 is a biomarker of malignant pancreatic intraductal papillary mucinous neoplasms. J Gastrointest Surg 13(11):1948–1954 (discussion 1954). doi: 10.1007/s11605-009-1001-9 Google Scholar
  9. 9.
    Bausch D, Thomas S, Mino-Kenudson M, Fernandez-del CC, Bauer TW, Williams M, Warshaw AL, Thayer SP, Kelly KA (2011) Plectin-1 as a novel biomarker for pancreatic cancer. Clin Cancer Res 17(2):302–309. doi: 10.1158/1078-0432.CCR-10-0999 PubMedCrossRefGoogle Scholar
  10. 10.
    Bolling MC, Pas HH, de Visser M, Aronica E, Pfendner EG, van den Berg MP, Diercks GF, Suurmeijer AJ, Jonkman MF (2010) PLEC1 mutations underlie adult-onset dilated cardiomyopathy in epidermolysis bullosa simplex with muscular dystrophy. J Invest Dermatol 130(4):1178–1181PubMedCrossRefGoogle Scholar
  11. 11.
    Burgstaller G, Gregor M, Winter L, Wiche G (2010) Keeping the vimentin network under control: cell-matrix adhesion-associated plectin 1f affects cell shape and polarity of fibroblasts. Mol Biol Cell 21(19):3362–3375PubMedCrossRefGoogle Scholar
  12. 12.
    Charlesworth A, Gagnoux-Palacios L, Bonduelle M, Ortonne JP, De Raeve L, Meneguzzi G (2003) Identification of a lethal form of epidermolysis bullosa simplex associated with a homozygous genetic mutation in plectin. J Invest Dermatol 121(6):1344–1348PubMedCrossRefGoogle Scholar
  13. 13.
    Chavanas S, Pulkkinen L, Gache Y, Smith FJ, McLean WH, Uitto J, Ortonne JP, Meneguzzi G (1996) A homozygous nonsense mutation in the PLEC1 gene in patients with epidermolysis bullosa simplex with muscular dystrophy. J Clin Invest 98(10):2196–2200. doi: 10.1172/JCI119028 PubMedCrossRefGoogle Scholar
  14. 14.
    Dang M, Pulkkinen L, Smith FJ, McLean WH, Uitto J (1998) Novel compound heterozygous mutations in the plectin gene in epidermolysis bullosa with muscular dystrophy and the use of protein truncation test for detection of premature termination codon mutations. Lab Invest 78(2):195–204PubMedGoogle Scholar
  15. 15.
    den Dunnen JT, Antonarakis SE (2000) Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat 15(1):7–12CrossRefGoogle Scholar
  16. 16.
    Eger A, Stockinger A, Wiche G, Foisner R (1997) Polarisation-dependent association of plectin with desmoplakin and the lateral submembrane skeleton in MDCK cells. J Cell Sci 110(Pt 11):1307–1316PubMedGoogle Scholar
  17. 17.
    Elliott CE, Becker B, Oehler S, Castañón MJ, Hauptmann R, Wiche G (1997) Plectin transcript diversity: identification and tissue distribution of variants with distinct first coding exons and rodless isoforms. Genomics 42(1):115–125PubMedCrossRefGoogle Scholar
  18. 18.
    Foisner R, Leichtfried FE, Herrmann H, Small JV, Lawson D, Wiche G (1988) Cytoskeleton-associated plectin: in situ localization, in vitro reconstitution, and binding to immobilized intermediate filament proteins. J Cell Biol 106(3):723–733PubMedCrossRefGoogle Scholar
  19. 19.
    Foisner R, Malecz N, Dressel N, Stadler C, Wiche G (1996) M-phase-specific phosphorylation and structural rearrangement of the cytoplasmic cross-linking protein plectin involve p34cdc2 kinase. Mol Biol Cell 7(2):273–288PubMedGoogle Scholar
  20. 20.
    Foisner R, Wiche G (1987) Structure and hydrodynamic properties of plectin molecules. J Mol Biol 198(3):515–531PubMedCrossRefGoogle Scholar
  21. 21.
    Forrest K, Mellerio JE, Robb S, Dopping-Hepenstal PJ, McGrath JA, Liu L, Buk SJ, Al-Sarraj S, Wraige E, Jungbluth H (2010) Congenital muscular dystrophy, myasthenic symptoms and epidermolysis bullosa simplex (EBS) associated with mutations in the PLEC1 gene encoding plectin. Neuromuscul Disord 20(11):709–711. pii:S0960-8966(10)00257-9Google Scholar
  22. 22.
    Fuchs E, Karakesisoglou I (2001) Bridging cytoskeletal intersections. Genes Dev 15(1):1–14PubMedCrossRefGoogle Scholar
  23. 23.
    Fuchs P, Spazierer D, Wiche G (2005) Plectin rodless isoform expression and its detection in mouse brain. Cell Mol Neurobiol 25(7):1141–1150. doi: 10.1007/s10571-005-7826-1 PubMedCrossRefGoogle Scholar
  24. 24.
    Fuchs P, Zörer M, Reipert S, Rezniczek GA, Propst F, Walko G, Fischer I, Bauer J, Leschnik MW, Luscher B, Thalhammer JG, Lassmann H, Wiche G (2009) Targeted inactivation of a developmentally regulated neural plectin isoform (plectin 1c) in mice leads to reduced motor nerve conduction velocity. J Biol Chem 284(39):26502–26509PubMedCrossRefGoogle Scholar
  25. 25.
    Fuchs P, Zörer M, Rezniczek GA, Spazierer D, Oehler S, Castañón MJ, Hauptmann R, Wiche G (1999) Unusual 5′ transcript complexity of plectin isoforms: novel tissue-specific exons modulate actin binding activity. Hum Mol Genet 8(13):2461–2472PubMedCrossRefGoogle Scholar
  26. 26.
    Gache Y, Chavanas S, Lacour JP, Wiche G, Owaribe K, Meneguzzi G, Ortonne JP (1996) Defective expression of plectin/HD1 in epidermolysis bullosa simplex with muscular dystrophy. J Clin Invest 97(10):2289–2298. doi: 10.1172/JCI118671 PubMedCrossRefGoogle Scholar
  27. 27.
    Garcia-Alvarez B, Bobkov A, Sonnenberg A, de Pereda JM (2003) Structural and functional analysis of the actin binding domain of plectin suggests alternative mechanisms for binding to F-actin and integrin beta4. Structure 11(6):615–625. pii:S096921260300090XGoogle Scholar
  28. 28.
    Gregor M, Zeöld A, Oehler S, Marobela KA, Fuchs P, Weigel G, Hardie DG, Wiche G (2006) Plectin scaffolds recruit energy-controlling AMP-activated protein kinase (AMPK) in differentiated myofibres. J Cell Sci 119(Pt 9):1864–1875PubMedCrossRefGoogle Scholar
  29. 29.
    Gundesli H, Talim B, Korkusuz P, Balci-Hayta B, Cirak S, Akarsu NA, Topaloglu H, Dincer P (2010) Mutation in exon 1f of PLEC, leading to disruption of plectin isoform 1f, causes autosomal-recessive limb-girdle muscular dystrophy. Am J Hum Genet 87(6):834–841. pii:S0002-9297(10)00533-1Google Scholar
  30. 30.
    Janda L, Damborsky J, Rezniczek GA, Wiche G (2001) Plectin repeats and modules: strategic cysteines and their presumed impact on cytolinker functions. BioEssays 23(11):1064–1069. doi: 10.1002/bies.1151 PubMedCrossRefGoogle Scholar
  31. 31.
    Jefferson JJ, Ciatto C, Shapiro L, Liem RK (2007) Structural analysis of the plakin domain of bullous pemphigoid antigen1 (BPAG1) suggests that plakins are members of the spectrin superfamily. J Mol Biol 366 (1):244-257. pii:S0022-2836(06)01576-2Google Scholar
  32. 32.
    Katada K, Tomonaga T, Satoh M, Matsushita K, Tonoike Y, Kodera Y, Hanazawa T, Nomura F, Okamoto Y (2012) Plectin promotes migration and invasion of cancer cells and is a novel prognostic marker for head and neck squamous cell carcinoma. J Proteomics 75(6):1803–1815. pii:S1874-3919(11)00699-3Google Scholar
  33. 33.
    Konieczny P, Fuchs P, Reipert S, Kunz WS, Zeöld A, Fischer I, Paulin D, Schröder R, Wiche G (2008) Myofiber integrity depends on desmin network targeting to Z-disks and costameres via distinct plectin isoforms. J Cell Biol 181(4):667–681PubMedCrossRefGoogle Scholar
  34. 34.
    Konieczny P, Wiche G (2008) Muscular integrity–a matter of interlinking distinct structures via plectin. Adv Exp Med Biol 642:165–175PubMedCrossRefGoogle Scholar
  35. 35.
    Koss-Harnes D, Hoyheim B, Anton-Lamprecht I, Gjesti A, Jorgensen RS, Jahnsen FL, Olaisen B, Wiche G, Gedde-Dahl T Jr (2002) A site-specific plectin mutation causes dominant epidermolysis bullosa simplex Ogna: two identical de novo mutations. J Invest Dermatol 118(1):87–93PubMedCrossRefGoogle Scholar
  36. 36.
    Koss-Harnes D, Hoyheim B, Jonkman MF, de Groot WP, de Weerdt CJ, Nikolic B, Wiche G, Gedde-Dahl T Jr (2004) Life-long course and molecular characterization of the original Dutch family with epidermolysis bullosa simplex with muscular dystrophy due to a homozygous novel plectin point mutation. Acta Derm Venereol 84(2):124–131PubMedCrossRefGoogle Scholar
  37. 37.
    Koster J, van Wilpe S, Kuikman I, Litjens SH, Sonnenberg A (2004) Role of binding of plectin to the integrin beta4 subunit in the assembly of hemidesmosomes. Mol Biol Cell 15(3):1211–1223. doi: 10.1091/mbc.E03-09-0697 PubMedCrossRefGoogle Scholar
  38. 38.
    Kunz M, Rouan F, Pulkkinen L, Hamm H, Jeschke R, Bruckner-Tuderman L, Brocker EB, Wiche G, Uitto J, Zillikens D (2000) Mutation reports: epidermolysis bullosa simplex associated with severe mucous membrane involvement and novel mutations in the plectin gene. J Invest Dermatol 114(2):376–380PubMedCrossRefGoogle Scholar
  39. 39.
    Lee KY, Liu YH, Ho CC, Pei RJ, Yeh KT, Cheng CC, Lai YS (2004) An early evaluation of malignant tendency with plectin expression in human colorectal adenoma and adenocarcinoma. J Med 35(1–6):141–149PubMedGoogle Scholar
  40. 40.
    Leung CL, Green KJ, Liem RK (2002) Plakins: a family of versatile cytolinker proteins. Trends Cell Biol 12(1):37–45PubMedCrossRefGoogle Scholar
  41. 41.
    Leung CL, Liem RK, Parry DA, Green KJ (2001) The plakin family. J Cell Sci 114(Pt 19):3409–3410PubMedGoogle Scholar
  42. 42.
    Liu CG, Maercker C, Castañón MJ, Hauptmann R, Wiche G (1996) Human plectin: organization of the gene, sequence analysis, and chromosome localization (8q24). Proc Natl Acad Sci USA 93(9):4278–4283PubMedCrossRefGoogle Scholar
  43. 43.
    Lu W, Schneider M, Neumann S, Jaeger VM, Taranum S, Munck M, Cartwright S, Richardson C, Carthew J, Noh K, Goldberg M, Noegel AA, Karakesisoglou I (2012) Nesprin interchain associations control nuclear size. Cell Mol Life Sci. doi: 10.1007/s00018-012-1034-1 Google Scholar
  44. 44.
    Lunter PC, Wiche G (2002) Direct binding of plectin to Fer kinase and negative regulation of its catalytic activity. Biochem Biophys Res Commun 296(4):904–910. pii:S0006291X02020077Google Scholar
  45. 45.
    Maiweilidan Y, Klauza I, Kordeli E (2011) Novel interactions of ankyrins-G at the costameres: the muscle-specific Obscurin/Titin-Binding-related Domain (OTBD) binds plectin and filamin C. Exp Cell Res 317(6):724–736. pii:S0014-4827(11)00004-8Google Scholar
  46. 46.
    Maselli R, Arredondo J, Cagney O, Mozaffar T, Skinner S, Yousif S, Davis R, Gregg J, Sivak M, Konia T, Thomas K, Wollmann R (2010) Congenital myasthenic syndrome associated with epidermolysis bullosa caused by homozygous mutations in PLEC1 and CHRNE. Clin Genet. doi: 10.1111/j.1399-0004.2010.01602.x PubMedGoogle Scholar
  47. 47.
    McInroy L, Maatta A (2011) Plectin regulates invasiveness of SW480 colon carcinoma cells and is targeted to podosome-like adhesions in an isoform-specific manner. Exp Cell Res 317(17):2468–2478. pii:S0014-4827(11)00299-0Google Scholar
  48. 48.
    McLean WH, Pulkkinen L, Smith FJ, Rugg EL, Lane EB, Bullrich F, Burgeson RE, Amano S, Hudson DL, Owaribe K, McGrath JA, McMillan JR, Eady RA, Leigh IM, Christiano AM, Uitto J (1996) Loss of plectin causes epidermolysis bullosa with muscular dystrophy: cDNA cloning and genomic organization. Genes Dev 10(14):1724–1735PubMedCrossRefGoogle Scholar
  49. 49.
    McMillan JR, Akiyama M, Rouan F, Mellerio JE, Lane EB, Leigh IM, Owaribe K, Wiche G, Fujii N, Uitto J, Eady RA, Shimizu H (2007) Plectin defects in epidermolysis bullosa simplex with muscular dystrophy. Muscle Nerve 35(1):24–35. doi: 10.1002/mus.20655 PubMedCrossRefGoogle Scholar
  50. 50.
    Mellerio JE, Smith FJ, McMillan JR, McLean WH, McGrath JA, Morrison GA, Tierney P, Albert DM, Wiche G, Leigh IM, Geddes JF, Lane EB, Uitto J, Eady RA (1997) Recessive epidermolysis bullosa simplex associated with plectin mutations: infantile respiratory complications in two unrelated cases. Br J Dermatol 137(6):898–906PubMedCrossRefGoogle Scholar
  51. 51.
    Nakamura H, Sawamura D, Goto M, McMillan JR, Park S, Kono S, Hasegawa S, Paku S, Nakamura T, Ogiso Y, Shimizu H (2005) Epidermolysis bullosa simplex associated with pyloric atresia is a novel clinical subtype caused by mutations in the plectin gene (PLEC1). J Mol Diagn 7(1):28–35. pii:S1525-1578(10)60005-0Google Scholar
  52. 52.
    Natsuga K, Nishie W, Akiyama M, Nakamura H, Shinkuma S, McMillan JR, Nagasaki A, Has C, Ouchi T, Ishiko A, Hirako Y, Owaribe K, Sawamura D, Bruckner-Tuderman L, Shimizu H (2010) Plectin expression patterns determine two distinct subtypes of epidermolysis bullosa simplex. Hum Mutat 31(3):308–316. doi: 10.1002/humu.21189 PubMedCrossRefGoogle Scholar
  53. 53.
    Natsuga K, Nishie W, Shinkuma S, Arita K, Nakamura H, Ohyama M, Osaka H, Kambara T, Hirako Y, Shimizu H (2010) Plectin deficiency leads to both muscular dystrophy and pyloric atresia in epidermolysis bullosa simplex. Hum Mutat 31(10):E1687–E1698. doi: 10.1002/humu.21330 PubMedCrossRefGoogle Scholar
  54. 54.
    Nikolic B, Mac Nulty E, Mir B, Wiche G (1996) Basic amino acid residue cluster within nuclear targeting sequence motif is essential for cytoplasmic plectin-vimentin network junctions. J Cell Biol 134(6):1455–1467PubMedCrossRefGoogle Scholar
  55. 55.
    Niwa T, Saito H, Imajoh-ohmi S, Kaminishi M, Seto Y, Miki Y, Nakanishi A (2009) BRCA2 interacts with the cytoskeletal linker protein plectin to form a complex controlling centrosome localization. Cancer Sci 100(11):2115–2125PubMedCrossRefGoogle Scholar
  56. 56.
    Ortega E, Buey RM, Sonnenberg A, de Pereda JM (2011) The structure of the plakin domain of plectin reveals a non-canonical SH3 domain interacting with its fourth spectrin repeat. J Biol Chem 286(14):12429–12438PubMedCrossRefGoogle Scholar
  57. 57.
    Osmanagic-Myers S, Gregor M, Walko G, Burgstaller G, Reipert S, Wiche G (2006) Plectin-controlled keratin cytoarchitecture affects MAP kinases involved in cellular stress response and migration. J Cell Biol 174(4):557–568PubMedCrossRefGoogle Scholar
  58. 58.
    Osmanagic-Myers S, Wiche G (2004) Plectin-RACK1 (receptor for activated C kinase 1) scaffolding: a novel mechanism to regulate protein kinase C activity. J Biol Chem 279(18):18701–18710PubMedCrossRefGoogle Scholar
  59. 59.
    Pawar H, Kashyap MK, Sahasrabuddhe NA, Renuse S, Harsha HC, Kumar P, Sharma J, Kandasamy K, Marimuthu A, Nair B, Rajagopalan S, Maharudraiah J, Premalatha CS, Kumar KV, Vijayakumar M, Chaerkady R, Prasad TS, Kumar RV, Pandey A (2011) Quantitative tissue proteomics of esophageal squamous cell carcinoma for novel biomarker discovery. Cancer Biol Ther 12(6):510–522PubMedCrossRefGoogle Scholar
  60. 60.
    Pfendner E, Rouan F, Uitto J (2005) Progress in epidermolysis bullosa: the phenotypic spectrum of plectin mutations. Exp Dermatol 14(4):241–249PubMedCrossRefGoogle Scholar
  61. 61.
    Pfendner E, Uitto J (2005) Plectin gene mutations can cause epidermolysis bullosa with pyloric atresia. J Invest Dermatol 124(1):111–115PubMedCrossRefGoogle Scholar
  62. 62.
    Pulkkinen L, Smith FJ, Shimizu H, Murata S, Yaoita H, Hachisuka H, Nishikawa T, McLean WH, Uitto J (1996) Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. Hum Mol Genet 5(10):1539–1546PubMedCrossRefGoogle Scholar
  63. 63.
    Reipert S, Steinböck F, Fischer I, Bittner RE, Zeöld A, Wiche G (1999) Association of mitochondria with plectin and desmin intermediate filaments in striated muscle. Exp Cell Res 252(2):479–491PubMedCrossRefGoogle Scholar
  64. 64.
    Rezniczek GA, Abrahamsberg C, Fuchs P, Spazierer D, Wiche G (2003) Plectin 5′-transcript diversity: short alternative sequences determine stability of gene products, initiation of translation and subcellular localization of isoforms. Hum Mol Genet 12(23):3181–3194PubMedCrossRefGoogle Scholar
  65. 65.
    Rezniczek GA, de Pereda JM, Reipert S, Wiche G (1998) Linking integrin alpha6beta4-based cell adhesion to the intermediate filament cytoskeleton: direct interaction between the beta4 subunit and plectin at multiple molecular sites. J Cell Biol 141(1):209–225PubMedCrossRefGoogle Scholar
  66. 66.
    Rezniczek GA, Konieczny P, Nikolic B, Reipert S, Schneller D, Abrahamsberg C, Davies KE, Winder SJ, Wiche G (2007) Plectin 1f scaffolding at the sarcolemma of dystrophic (mdx) muscle fibers through multiple interactions with beta-dystroglycan. J Cell Biol 176(7):965–977PubMedCrossRefGoogle Scholar
  67. 67.
    Rezniczek GA, Walko G, Wiche G (2010) Plectin gene defects lead to various forms of epidermolysis bullosa simplex. Dermatol Clin 28(1):33–41. pii:S0733-8635(09)00078-3Google Scholar
  68. 68.
    Rouan F, Pulkkinen L, Meneguzzi G, Laforgia S, Hyde P, Kim DU, Richard G, Uitto J (2000) Epidermolysis bullosa: novel and de novo premature termination codon and deletion mutations in the plectin gene predict late-onset muscular dystrophy. J Invest Dermatol 114(2):381–387PubMedCrossRefGoogle Scholar
  69. 69.
    Ruhrberg C, Watt FM (1997) The plakin family: versatile organizers of cytoskeletal architecture. Curr Opin Genet Dev 7(3):392–397. pii:S0959-437X(97)80154-2Google Scholar
  70. 70.
    Sawamura D, Goto M, Sakai K, Nakamura H, McMillan JR, Akiyama M, Shirado O, Oyama N, Satoh M, Kaneko F, Takahashi T, Konno H, Shimizu H (2007) Possible involvement of exon 31 alternative splicing in phenotype and severity of epidermolysis bullosa caused by mutations in PLEC1. J Invest Dermatol 127(6):1537–1540PubMedCrossRefGoogle Scholar
  71. 71.
    Schara U, Tucke J, Mortier W, Nusslein T, Rouan F, Pfendner E, Zillikens D, Bruckner-Tuderman L, Uitto J, Wiche G, Schröder R (2004) Severe mucous membrane involvement in epidermolysis bullosa simplex with muscular dystrophy due to a novel plectin gene mutation. Eur J Pediatr 163(4–5):218–222. doi: 10.1007/s00431-004-1410-4 PubMedCrossRefGoogle Scholar
  72. 72.
    Schröder R, Kunz WS, Rouan F, Pfendner E, Tolksdorf K, Kappes-Horn K, Altenschmidt-Mehring M, Knoblich R, van der Ven PF, Reimann J, Furst DO, Blumcke I, Vielhaber S, Zillikens D, Eming S, Klockgether T, Uitto J, Wiche G, Rolfs A (2002) Disorganization of the desmin cytoskeleton and mitochondrial dysfunction in plectin-related epidermolysis bullosa simplex with muscular dystrophy. J Neuropathol Exp Neurol 61(6):520–530PubMedGoogle Scholar
  73. 73.
    Schröder R, Schoser B (2009) Myofibrillar myopathies: a clinical and myopathological guide. Brain Pathol 19(3):483–492PubMedCrossRefGoogle Scholar
  74. 74.
    Seifert GJ, Lawson D, Wiche G (1992) Immunolocalization of the intermediate filament-associated protein plectin at focal contacts and actin stress fibers. Eur J Cell Biol 59(1):138–147PubMedGoogle Scholar
  75. 75.
    Selcen D, Juel VC, Hobson-Webb LD, Smith EC, Stickler DE, Bite AV, Ohno K, Engel AG (2011) Myasthenic syndrome caused by plectinopathy. Neurology 76(4):327–336PubMedCrossRefGoogle Scholar
  76. 76.
    Sevcik J, Urbanikova L, Kostan J, Janda L, Wiche G (2004) Actin-binding domain of mouse plectin. Crystal structure and binding to vimentin. Eur J Biochem 271(10):1873–1884. doi: 10.1111/j.1432-1033.2004.04095.x Google Scholar
  77. 77.
    Shimizu H, Masunaga T, Kurihara Y, Owaribe K, Wiche G, Pulkkinen L, Uitto J, Nishikawa T (1999) Expression of plectin and HD1 epitopes in patients with epidermolysis bullosa simplex associated with muscular dystrophy. Arch Dermatol Res 291(10):531–537PubMedCrossRefGoogle Scholar
  78. 78.
    Smith FJ, Eady RA, Leigh IM, McMillan JR, Rugg EL, Kelsell DP, Bryant SP, Spurr NK, Geddes JF, Kirtschig G, Milana G, de Bono AG, Owaribe K, Wiche G, Pulkkinen L, Uitto J, McLean WH, Lane EB (1996) Plectin deficiency results in muscular dystrophy with epidermolysis bullosa. Nat Genet 13(4):450–457. doi: 10.1038/ng0896-450 PubMedCrossRefGoogle Scholar
  79. 79.
    Sonnenberg A, Liem RK (2007) Plakins in development and disease. Exp Cell Res 313(10):2189–2203PubMedCrossRefGoogle Scholar
  80. 80.
    Spurny R, Gregor M, Castañón MJ, Wiche G (2008) Plectin deficiency affects precursor formation and dynamics of vimentin networks. Exp Cell Res 314(19):3570–3580. pii:S0014-4827(08)00363-7Google Scholar
  81. 81.
    Steinböck FA, Nikolic B, Coulombe PA, Fuchs E, Traub P, Wiche G (2000) Dose-dependent linkage, assembly inhibition and disassembly of vimentin and cytokeratin 5/14 filaments through plectin’s intermediate filament-binding domain. J Cell Sci 113(Pt 3):483–491PubMedGoogle Scholar
  82. 82.
    Steinböck FA, Wiche G (1999) Plectin: a cytolinker by design. Biol Chem 380(2):151–158. doi: 10.1515/BC.1999.023 PubMedCrossRefGoogle Scholar
  83. 83.
    Takahashi Y, Rouan F, Uitto J, Ishida-Yamamoto A, Iizuka H, Owaribe K, Tanigawa M, Ishii N, Yasumoto S, Hashimoto T (2005) Plectin deficient epidermolysis bullosa simplex with 27-year-history of muscular dystrophy. J Dermatol Sci 37(2):87–93. pii:S0923-1811(04)00260-9Google Scholar
  84. 84.
    Takizawa Y, Shimizu H, Rouan F, Kawai M, Udono M, Pulkkinen L, Nishikawa T, Uitto J (1999) Four novel plectin gene mutations in Japanese patients with epidermolysis bullosa with muscular dystrophy disclosed by heteroduplex scanning and protein truncation tests. J Invest Dermatol 112(1):109–112. doi: 10.1046/j.1523-1747.1999.00461.x PubMedCrossRefGoogle Scholar
  85. 85.
    Thomsen C, Udhane S, Runnberg R, Wiche G, Stahlberg A, Aman P (2012) Fused in sarcoma (FUS) interacts with the cytolinker protein plectin: implications for FUS subcellular localization and function. Exp Cell Res 318(5):653–661. pii:S0014-4827(11)00500-3Google Scholar
  86. 86.
    Tian R, Gregor M, Wiche G, Goldman JE (2006) Plectin regulates the organization of glial fibrillary acidic protein in Alexander disease. Am J Pathol 168(3):888–897PubMedCrossRefGoogle Scholar
  87. 87.
    Uitto J, Pfendner E (2004) Compound heterozygosity of unique in-frame insertion and deletion mutation in the plectin gene in a mild case of epidermolysis bullosa with very late onset muscular dystrophy. J Invest Dermatol 122:A86Google Scholar
  88. 88.
    Walko G, Vukasinovic N, Gross K, Fischer I, Sibitz S, Fuchs P, Reipert S, Jungwirth U, Berger W, Salzer U, Carugo O, Castañón MJ, Wiche G (2011) Targeted proteolysis of plectin isoform 1a accounts for hemidesmosome dysfunction in mice mimicking the dominant skin blistering disease EBS-Ogna. PLoS Genet 7(12):e1002396. doi: 10.1371/journal.pgen.1002396 PubMedCrossRefGoogle Scholar
  89. 89.
    Weitzer G, Wiche G (1987) Plectin from bovine lenses. Chemical properties, structural analysis and initial identification of interaction partners. Eur J Biochem 169(1):41–52PubMedCrossRefGoogle Scholar
  90. 90.
    Wiche G (1989) Plectin: general overview and appraisal of its potential role as a subunit protein of the cytomatrix. Crit Rev Biochem Mol Biol 24(1):41–67. doi: 10.3109/10409238909082551 PubMedCrossRefGoogle Scholar
  91. 91.
    Wiche G (1998) Role of plectin in cytoskeleton organization and dynamics. J Cell Sci 111:2477–2486PubMedGoogle Scholar
  92. 92.
    Wiche G, Becker B, Luber K, Weitzer G, Castañón MJ, Hauptmann R, Stratowa C, Stewart M (1991) Cloning and sequencing of rat plectin indicates a 466-kD polypeptide chain with a three-domain structure based on a central alpha-helical coiled coil. J Cell Biol 114(1):83–99PubMedCrossRefGoogle Scholar
  93. 93.
    Wiche G, Krepler R, Artlieb U, Pytela R, Aberer W (1984) Identification of plectin in different human cell types and immunolocalization at epithelial basal cell surface membranes. Exp Cell Res 155(1):43–49PubMedCrossRefGoogle Scholar
  94. 94.
    Wiche G, Krepler R, Artlieb U, Pytela R, Denk H (1983) Occurrence and immunolocalization of plectin in tissues. J Cell Biol 97(3):887–901PubMedCrossRefGoogle Scholar
  95. 95.
    Wiche G, Winter L (2011) Plectin isoforms as organizers of intermediate filament cytoarchitecture. Bioarchitecture 1(1):14–20. doi: 10.4161/bioa.1.1.14630 Google Scholar
  96. 96.
    Wilhelmsen K, Litjens SH, Kuikman I, Tshimbalanga N, Janssen H, van den Bout I, Raymond K, Sonnenberg A (2005) Nesprin-3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin. J Cell Biol 171(5):799–810PubMedCrossRefGoogle Scholar
  97. 97.
    Winter L, Abrahamsberg C, Wiche G (2008) Plectin isoform 1b mediates mitochondrion-intermediate filament network linkage and controls organelle shape. J Cell Biol 181(6):903–911PubMedCrossRefGoogle Scholar
  98. 98.
    Yiu EM, Klausegger A, Waddell LB, Grasern N, Lloyd L, Tran K, North KN, Bauer JW, McKelvie P, Chow CW, Ryan MM, Murrell DF (2011) Epidermolysis bullosa with late-onset muscular dystrophy and plectin deficiency. Muscle Nerve 44(1):135–141. doi: 10.1002/mus.22076 PubMedCrossRefGoogle Scholar
  99. 99.
    Zhang T, Haws P, Wu Q (2004) Multiple variable first exons: a mechanism for cell- and tissue-specific gene regulation. Genome Res 14(1):79–89. doi: 10.1101/gr.1225204 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Department of Biochemistry and Cell Biology, Max F. Perutz LaboratoriesUniversity of ViennaViennaAustria

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