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01.03.2009 | Original Paper

Differential involvement of sarcomeric proteins in myofibrillar myopathies: a morphological and immunohistochemical study

verfasst von: Kristl G. Claeys, Peter F. M. van der Ven, Anthony Behin, Tanya Stojkovic, Bruno Eymard, Odile Dubourg, Pascal Laforêt, Georgine Faulkner, Pascale Richard, Patrick Vicart, Norma B. Romero, Gisela Stoltenburg, Bjarne Udd, Michel Fardeau, Thomas Voit, Dieter O. Fürst

Erschienen in: Acta Neuropathologica | Ausgabe 3/2009

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Abstract

Myofibrillar myopathies (MFMs) are rare inherited or sporadic progressive neuromuscular disorders with considerable clinical and genetic heterogeneity. In the current study, we have analyzed histopathological and immunohistochemical characteristics in genetically identified MFMs. We performed a morphological and morphometrical study in a cohort of 24 genetically identified MFM patients (12 desmin, 6 αB-crystallin, 4 ZASP, 2 myotilin), and an extensive immunohistochemical study in 15 of these patients, using both well-known and novel antibodies directed against distinct compartments of the muscle fibers, including Z-disc and M-band proteins. Our morphological data revealed some significant differences between the distinct MFM subgroups: the consistent presence of ‘rubbed-out’ fibers in desminopathies and αB-crystallinopathies, an elevated frequency of vacuoles in ZASPopathies and myotilinopathies, and the presence of a few necrotic fibers in the two myotilinopathy patients. Immunohistochemistry showed that in MFM only a subset of Z-disc proteins, such as filamin C and its ligands myotilin and Xin, exhibited significant alterations in their localization, whereas other Z-disc proteins like α-actinin, myopodin and tritopodin, did not. In contrast, M-band proteins revealed no abnormalities in MFM. We conclude that the presence of ‘rubbed-out’ fibers are a suggestive feature for desminopathy or αB-crystallinopathy, and that MFM is not a general disease of the myofibril, but primarily affects a subgroup of stress-responsive Z-disc proteins.

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Baeta AM, Figarella-Branger D, Bille-Turc F, Lepidi H, Pellissier JF (1996) Familial desmin myopathies and cytoplasmic body myopathies. Acta Neuropathol 92:499–510. doi:10.1007/s004010050552 PubMedCrossRef

Bohlega S, Lach B, Meyer BF et al (2003) Autosomal dominant hyaline body myopathy: clinical variability and pathologic findings. Neurology 61:1519–1523PubMed

Brooke MH, Engel WK (1969) The histographic analysis of human muscle biopsies with regard to fiber types 1. Adult male and female. Neurology 19:221–233PubMed

Choi S, Gustafson-Wagner EA, Wang Q et al (2007) The intercalated disk protein, mXinalpha, is capable of interacting with beta-catenin and bundling actin filaments. J Biol Chem 282:36024–36036. doi:10.1074/jbc.M707639200 PubMedCrossRef

Claeys KG, Fardeau M, Schröder R et al (2008) Electron microscopy in myofibrillar myopathies reveals clues to the mutated gene. Neuromuscul Disord 18:656–666. doi:10.1016/j.nmd.2008.06.367 PubMedCrossRef

Davies KE, Nowak KJ (2006) Molecular mechanisms of muscular dystrophies: old and new players. Nat Rev Mol Cell Biol 7:762–773. doi:10.1038/nrm2024 PubMedCrossRef

De Bleecker J, Engel AG, Ertl BB (1996) Myofibrillar myopathy with abnormal foci of desmin positivity II. Immunocytochemical analysis reveals accumulation of multiple other proteins. J Neuropathol Exp Neurol 55:563–577. doi:10.1097/00005072-199605000-00009 PubMedCrossRef

Dubowitz V, Sewry CA (2007) Muscle biopsy: a practical approach, 3rd edn. Elsevier, London

Fardeau M, Godet-Guillain J, Tome FM et al (1978) A new familial muscular disorder demonstrated by the intra-sarcoplasmic accumulation of a granulo-filamentous material which is dense on electron microscopy. Rev Neurol (Paris) 134:411–425 in French

10.

Faulkner G, Pallavicini A, Formentin E et al (1999) ZASP: a new Z-band alternatively spliced PDZ-motif protein. J Cell Biol 146:465–475PubMedCrossRef

11.

Fayet G, Rouche A, Hogrel JY, Tomé FM, Fardeau M (2001) Age-related morphological changes of the deltoid muscle from 50 to 79 years of age. Acta Neuropathol 101:358–366PubMed

12.

Frank D, Kuhn C, Katus HA, Frey N (2006) The sarcomeric Z-disc: a nodal point in signalling and disease. J Mol Med 84:446–468PubMedCrossRef

13.

Frey N, Barrientos T, Shelton JM et al (2004) Mice lacking calsarcin-1 are sensitized to calcineurin signaling and show accelerated cardiomyopathy in response to pathological biomechanical stress. Nat Med 10:1336–1343PubMedCrossRef

14.

Fukuzawa A, Lange S, Holt M et al (2008) Interactions with titin and myomesin target obscurin and obscurin-like 1 to the M-band: implications for hereditary myopathies. J Cell Sci 121:1841–1851PubMedCrossRef

15.

Fürst DO, Osborn M, Nave R, Weber K (1988) The organization of titin filaments in the half-sarcomere revealed by monoclonal antibodies in immunoelectron microscopy: a map of ten nonrepetitive epitopes starting at the Z line extends close to the M line. J Cell Biol 106:1563–1572PubMedCrossRef

16.

Goldfarb LG, Park KY, Cervenakova L et al (1998) Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Nat Genet 19:402–403PubMedCrossRef

17.

Gontier Y, Taivainen A, Fontao L et al (2005) The Z-disc proteins myotilin and FATZ-1 interact with each other and are connected to the sarcolemma via muscle-specific filamins. J Cell Sci 118:3739–3749PubMedCrossRef

18.

Griggs R, Vihola A, Hackman P et al (2007) Zaspopathy in a large classic late-onset distal myopathy family. Brain 130:1477–1484PubMedCrossRef

19.

Hauser MA, Horrigan SK, Salmikangas P et al (2000) Myotilin is mutated in limb girdle muscular dystrophy 1A. Hum Mol Genet 9:2141–2147PubMedCrossRef

20.

Hawke TJ, Atkinson DJ, Kanatous SB, van der Ven PFM, Goetsch SC, Garry DJ (2007) Xin, an actin binding protein, is expressed within muscle satellite cells and newly regenerated skeletal muscle fibers. Am J Physiol Cell Physiol 293:C1636–C1644PubMedCrossRef

21.

Hijikata T, Murakami T, Imamura M, Fujimaki N, Ishikawa H (1999) Plectin is a linker of intermediate filaments to Z-discs in skeletal muscle fibers. J Cell Sci 112:867–876PubMed

22.

Hijikata T, Murakami T, Ishikawa H, Yorifuji H (2003) Plectin tethers desmin intermediate filaments onto subsarcolemmal dense plaques containing dystrophin and vinculin. Histochem Cell Biol 119:109–123PubMed

23.

Huang HT, Brand OM, Mathew M et al (2006) Myomaxin is a novel transcriptional target for MEF2A that encodes a Xin related alpha-actinin interacting protein. J Biol Chem 281:39370–39379PubMedCrossRef

24.

Kley RA, Hellenbroich Y, van der Ven PFM et al (2007) Clinical and morphological phenotype of the filamin myopathy: a study of 31 German patients. Brain 130:3250–3264PubMedCrossRef

25.

Knöll R, Hoshijima M, Hoffman HM et al (2002) The cardiac mechanical stretch sensor machinery involves a Z-disc complex that is defective in a subset of human dilated cardiomyopathy. Cell 111:943–955PubMedCrossRef

26.

Li Z, Colucci-Guyon E, Pinçon-Raymond M et al (1996) Cardiovascular lesions and skeletal myopathy in mice lacking desmin. Dev Biol 175:362–366PubMedCrossRef

27.

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

28.

Nakano S, Engel AG, Akiguchi I, Kimura J (1997) Myofibrillar myopathy III. Abnormal expression of cyclin-dependent kinases and nuclear proteins. J Neuropathol Exp Neurol 56:850–856PubMedCrossRef

29.

Nakano S, Engel AG, Waclawik AJ, Emslie-Smith AM, Busis NA (1996) Myofibrillar myopathy with abnormal foci of desmin positivity I. Light and electron microscopy analysis of 10 cases. J Neuropathol Exp Neurol 55:549–562PubMedCrossRef

30.

Olivé M, Goldfarb LG, Shatunov A, Fischer D, Ferrer I (2005) Myotilinopathy: refining the clinical and myopathological phenotype. Brain 128:2315–2326PubMedCrossRef

31.

Pacholsky D, Vakeel P, Himmel M et al (2004) Xin repeats define a novel actin-binding motif. J Cell Sci 117:5257–5268PubMedCrossRef

32.

Pénisson-Besnier I, Talvinen K, Dumez C et al (2006) Myotilinopathy in a family with late onset myopathy. Neuromuscul Disord 16:427–431PubMedCrossRef

33.

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 277:3433–3439PubMedCrossRef

34.

Quinzii CM, Vu TH, Min KC et al (2008) X-linked dominant scapuloperoneal myopathy is due to a mutation in the gene encoding four-and-a-half-LIM protein 1. Am J Hum Genet 82:208–213PubMedCrossRef

35.

Reimann J, Kunz WS, Vielhaber S, Kappes-Horn K, Schröder R (2003) Mitochondrial dysfunction in myofibrillar myopathy. Neuropathol Appl Neurobiol 29:45–51PubMedCrossRef

36.

Rezniczek GA, Konieczny P, Nikolic B et al (2007) Plectin 1f scaffolding at the sarcolemma of dystrophic (mdx) muscle fibers through multiple interactions with beta-dystroglycan. J Cell Biol 176:965–977PubMedCrossRef

37.

Salmikangas P, Mykkänen OM, Grönholm M, Heiska L, Kere J, Carpén O (1999) Myotilin, a novel sarcomeric protein with two Ig-like domains, is encoded by a candidate gene for limb-girdle muscular dystrophy. Hum Mol Genet 8:1329–1336PubMedCrossRef

38.

Schröder R, Goudeau B, Simon MC et al (2003) On noxious desmin: functional effects of a novel heterozygous desmin insertion mutation on the extrasarcomeric desmin cytoskeleton and mitochondria. Hum Mol Genet 12:657–669PubMedCrossRef

39.

Selcen D (2008) Myofibrillar myopathies. Curr Opin Neurol 21:585–589PubMedCrossRef

40.

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

41.

Selcen D, Engel AG (2004) Mutations in myotilin cause myofibrillar myopathy. Neurology 62:1363–1371PubMed

42.

Selcen D, Engel AG (2005) Mutations in ZASP define a novel form of muscular dystrophy in humans. Ann Neurol 57:269–276PubMedCrossRef

43.

Selcen D, Ohno K, Engel AG (2004) Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients. Brain 127:439–451PubMedCrossRef

44.

Sinn HW, Balsamo J, Lilien J, Lin JJ (2002) Localization of the novel Xin protein to the adherens junction complex in cardiac and skeletal muscle during development. Dev Dyn 225:1–13PubMedCrossRef

45.

Thompson TG, Chan YM, Hack AA et al (2000) Filamin 2 (FLN2): a muscle-specific sarcoglycan interacting protein. Cell Biol 148:115–126CrossRef

46.

van der Ven PFM, Ehler E, Vakeel P et al (2006) Unusual splicing events result in distinct Xin isoforms that associate differentially with filamin C and Mena/VASP. Exp Cell Res 312:2154–2167PubMedCrossRef

47.

van der Ven PFM, Obermann WMJ, Lemke B, Gautel M, Weber K, Fürst DO (2000) Characterization of muscle filamin isoforms suggests a possible role of gamma-filamin/ABP-L in sarcomeric Z-disc formation. Cell Motil Cytoskeleton 45:149–162PubMedCrossRef

48.

van der Ven PFM, Wiesner S, Salmikangas P et al (2000) Indications for a novel muscular dystrophy pathway. gamma-filamin, the muscle-specific filamin isoform, interacts with myotilin. J Cell Biol 151:235–248PubMedCrossRef

49.

Vicart P, Caron A, Guicheney P et al (1998) A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet 20:92–95PubMedCrossRef

50.

Vinkemeier U, Obermann W, Weber K, Fürst DO (1993) The globular head domain of titin extends into the center of the sarcomeric M band. cDNA cloning, epitope mapping and immunoelectron microscopy of two titin-associated proteins. J Cell Sci 106:319–330PubMed

51.

Vorgerd M, van der Ven PFM, Bruchertseifer V et al (2005) A mutation in the dimerization domain of filamin C causes a novel type of autosomal dominant myofibrillar myopathy. Am J Hum Genet 77:297–304PubMedCrossRef

52.

Weins A, Schwarz K, Faul C, Barisoni L, Linke WA, Mundel P (2001) Differentiation- and stress-dependent nuclear cytoplasmic redistribution of myopodin, a novel actin-bundling protein. J Cell Biol 155:393–404PubMedCrossRef

Titel: Differential involvement of sarcomeric proteins in myofibrillar myopathies: a morphological and immunohistochemical study
verfasst von: Kristl G. Claeys
Peter F. M. van der Ven
Anthony Behin
Tanya Stojkovic
Bruno Eymard
Odile Dubourg
Pascal Laforêt
Georgine Faulkner
Pascale Richard
Patrick Vicart
Norma B. Romero
Gisela Stoltenburg
Bjarne Udd
Michel Fardeau
Thomas Voit
Dieter O. Fürst
Publikationsdatum: 01.03.2009
Verlag: Springer-Verlag
Erschienen in: Acta Neuropathologica / Ausgabe 3/2009
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-008-0479-7

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