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Laminopathies

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Cytoskeleton and Human Disease

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Abstract

The laminopathies are a group of rare diseases characterized by a vast range of phenotypic alterations, due to mutations in lamin A and C or other nuclear envelope proteins. A-type lamins, as well as B-type lamins, belong to the type V intermediate filaments and, by polymerization, form the nuclear lamina, a component of the nuclear envelope. Following a brief description of the complex interactions between lamins and proteins of the nuclear membrane, this Chapter describes disease phenotypes that characterize each laminopathy, the possible mechanisms involved into the pathogenesis, as well as potential therapies based on the use of existing drugs.

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References

  1. Fisher DZ, Chaudhary N, Blobel G (1986) cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins. Proc Natl Acad Sci U S A 83:6450–6454

    Article  PubMed  CAS  Google Scholar 

  2. Kuga T, Nozaki N, Matsushita K et al (2010) Phosphorylation statuses at different residues of lamin B2, B1, and A/C dynamically and independently change throughout the cell cycle. Exp Cell Res 316:2301–2312

    Article  PubMed  CAS  Google Scholar 

  3. Maraldi NM, Squarzoni S, Sabatelli P et al (2005) Laminopathies: involvement of structural nuclear proteins in the pathogenesis of an increasing number of human diseases. J Cell Physiol 203:319–327

    Article  PubMed  CAS  Google Scholar 

  4. Prokocimer M, Davidovich M, Nissim-Rafinia M et al (2009) Nuclear lamins: key regulators of nuclear structure and activities. J Cell Mol Med 13:1059–1085

    Article  PubMed  CAS  Google Scholar 

  5. Schneider M, Lu W, Neumann S et al (2010) Molecular mechanisms of centrosome and cytoskeleton anchorage at the nuclear envelope. Cell Mol Life Sci

    Google Scholar 

  6. Kapinos LE, Schumacher J, Mucke N et al (2010) Characterization of the head-to-tail overlap complexes formed by human lamin A, B1 and B2 “half-minilamin” dimers. J Mol Biol 396:719–731

    Article  PubMed  CAS  Google Scholar 

  7. Vergnes L, Peterfy M, Bergo MO et al (2004) Lamin B1 is required for mouse development and nuclear integrity. Proc Natl Acad Sci U S A 101:10428–10433

    Article  PubMed  CAS  Google Scholar 

  8. Malhas A, Lee CF, Sanders R et al (2007) Defects in lamin B1 expression or processing affect interphase chromosome position and gene expression. J Cell Biol 176:593–603

    Article  PubMed  CAS  Google Scholar 

  9. Barrowman J, Hamblet C, George CM et al (2008) Analysis of prelamin A biogenesis reveals the nucleus to be a CaaX processing compartment. Mol Biol Cell 19:5398–5408

    Article  PubMed  CAS  Google Scholar 

  10. Dominici S, Fiori V, Magnani M et al (2009) Different prelamin A forms accumulate in human fibroblasts: a study in experimental models and progeria. Eur J Histochem 53:43–52

    PubMed  CAS  Google Scholar 

  11. Bione S, Maestrini E, Rivella S et al (1994) Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy. Nat Genet 8:323–327

    Article  PubMed  CAS  Google Scholar 

  12. Bonne G, Di Barletta MR, Varnous S et al (1999) Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. Nat Genet 21:285–288

    Article  PubMed  CAS  Google Scholar 

  13. Emery AE (2000) Emery-Dreifuss muscular dystrophy—a 40 year retrospective. Neuromuscul Disord 10:228–232

    Article  PubMed  CAS  Google Scholar 

  14. Worman HJ, Ostlund C, Wang Y (2010) Diseases of the nuclear envelope. Cold Spring Harb Perspect Biol 2:a000760

    Article  PubMed  CAS  Google Scholar 

  15. Raffaele Di, Barletta M, Ricci E, Galluzzi G et al (2000) Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy. Am J Hum Genet 66:1407–1412

    Article  Google Scholar 

  16. Muchir A, Bonne G, Van Der Kooi AJ et al (2000) Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B). Hum Mol Genet 9:1453–1459

    Article  PubMed  CAS  Google Scholar 

  17. Fatkin D, MacRae C, Sasaki T et al (1999) Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. N Engl J Med 341:1715–1724

    Article  PubMed  CAS  Google Scholar 

  18. Shackleton S, Lloyd DJ, Jackson SN et al (2000) LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat Genet 24:153–156

    Article  PubMed  CAS  Google Scholar 

  19. De Sandre-Giovannoli A, Chaouch M, Kozlov S et al (2002) Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse. Am J Hum Genet 70:726–736

    Article  PubMed  CAS  Google Scholar 

  20. Eriksson M, Brown WT, Gordon LB et al (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423:293–298

    Article  PubMed  CAS  Google Scholar 

  21. De Sandre-Giovannoli A, Bernard R, Cau P et al (2003) Lamin a truncation in Hutchinson-Gilford progeria. Science 300:2055

    Article  PubMed  CAS  Google Scholar 

  22. Chen L, Lee L, Kudlow BA et al (2003) LMNA mutations in atypical Werner’s syndrome. Lancet 362:440–445

    Article  PubMed  CAS  Google Scholar 

  23. Garg A, Subramanyam L, Agarwal AK et al (2009) Atypical progeroid syndrome due to heterozygous missense LMNA mutations. J Clin Endocrinol Metab 94:4971–4983

    Article  PubMed  CAS  Google Scholar 

  24. Novelli G, Muchir A, Sangiuolo F et al (2002) Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. Am J Hum Genet 71:426–431

    Article  PubMed  CAS  Google Scholar 

  25. Navarro CL, Cadinanos J, De Sandre-Giovannoli A et al (2005) Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of Lamin A precursors. Hum Mol Genet 14:1503–1513

    Article  PubMed  CAS  Google Scholar 

  26. van Engelen BG, Muchir A, Hutchison CJ et al (2005) The lethal phenotype of a homozygous nonsense mutation in the lamin A/C gene. Neurology 64:374–376

    Article  PubMed  CAS  Google Scholar 

  27. Brodsky GL, Muntoni F, Miocic S et al (2000) Lamin A/C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement. Circulation 101:473–476

    Article  PubMed  CAS  Google Scholar 

  28. Araujo-Vilar D, Lado-Abeal J, Palos-Paz F et al (2008) A novel phenotypic expression associated with a new mutation in LMNA gene, characterized by partial lipodystrophy, insulin resistance, aortic stenosis and hypertrophic cardiomyopathy. Clin Endocrinol (Oxf) 69:61–68

    Article  CAS  Google Scholar 

  29. Lombardi F, Gullotta F, Columbaro M et al (2007) Compound heterozygosity for mutations in LMNA in a patient with a myopathic and lipodystrophic mandibuloacral dysplasia type A Phenotype. J Clin Endocrinol Metab 92:4467–4471

    Article  PubMed  CAS  Google Scholar 

  30. Rankin J, Ellard S (2006) The laminopathies: a clinical review. Clin Genet 70:261–274

    Article  PubMed  CAS  Google Scholar 

  31. Carboni N, Mura M, Marrosu G et al (2010) Muscle imaging analogies in a cohort of patients with different clinical phenotypes caused by LMNA gene mutations. Muscle Nerve 41:458–463

    Article  PubMed  CAS  Google Scholar 

  32. Sabatelli P, Lattanzi G, Ognibene A et al (2001) Nuclear alterations in autosomal-dominant Emery-Dreifuss muscular dystrophy. Muscle Nerve 24:826–829

    Article  PubMed  CAS  Google Scholar 

  33. Cenni V, Sabatelli P, Mattioli E et al (2005) Lamin A N-terminal phosphorylation is associated with myoblast activation: impairment in Emery-Dreifuss muscular dystrophy. J Med Genet 42:214–220

    Article  PubMed  CAS  Google Scholar 

  34. Maraldi NM, Lattanzi G, Capanni C et al (2006) Nuclear envelope proteins and chromatin arrangement: a pathogenic mechanism for laminopathies. Eur J Histochem 50:1–8

    PubMed  CAS  Google Scholar 

  35. Capanni C, Mattioli E, Columbaro M et al (2005) Altered pre-lamin A processing is a common mechanism leading to lipodystrophy. Hum Mol Genet 14:1489–1502

    Article  PubMed  CAS  Google Scholar 

  36. Prigogine C, Richard P, Van Den Bergh P et al (2010) Novel LMNA mutation presenting as severe congenital muscular dystrophy. Pediatr Neurol 43:283–286

    Article  PubMed  Google Scholar 

  37. Quijano-Roy S, Mbieleu B, Bonnemann CG et al (2008) De novo LMNA mutations cause a new form of congenital muscular dystrophy. Ann Neurol 64:177–186

    Article  PubMed  Google Scholar 

  38. D’Amico A, Haliloglu G, Richard P et al (2005) Two patients with ’Dropped head syndrome’ due to mutations in LMNA or SEPN1 genes. Neuromuscul Disord 15:521–524

    Article  PubMed  Google Scholar 

  39. Boriani G, Gallina M, Merlini L et al (2003) Clinical relevance of atrial fibrillation/flutter, stroke, pacemaker implant, and heart failure in Emery-Dreifuss muscular dystrophy: a long-term longitudinal study. Stroke 34:901–908

    Article  PubMed  Google Scholar 

  40. Sylvius N, Tesson F (2006) Lamin A/C and cardiac diseases. Curr Opin Cardiol 21:159–165

    Article  PubMed  Google Scholar 

  41. Renou L, Stora S, Yaou RB et al (2008) Heart-hand syndrome of Slovenian type: a new kind of laminopathy. J Med Genet 45:666–671

    Article  PubMed  CAS  Google Scholar 

  42. Cao H, Hegele RA (2000) Nuclear lamin A/C R482Q mutation in canadian kindreds with Dunnigan-type familial partial lipodystrophy. Hum Mol Genet 9:109–112

    Article  PubMed  CAS  Google Scholar 

  43. Araujo-Vilar D, Lattanzi G, Gonzalez-Mendez B et al (2009) Site-dependent differences in both prelamin A and adipogenic genes in subcutaneous adipose tissue of patients with type 2 familial partial lipodystrophy. J Med Genet 46:40–48

    Article  PubMed  CAS  Google Scholar 

  44. Morel CF, Thomas MA, Cao H et al (2006) A LMNA splicing mutation in two sisters with severe Dunnigan-type familial partial lipodystrophy type 2. J Clin Endocrinol Metab 91:2689–2695

    Article  PubMed  CAS  Google Scholar 

  45. Hennekam RC (2006) Hutchinson-Gilford progeria syndrome: review of the phenotype. Am J Med Genet A 140:2603–2624

    PubMed  Google Scholar 

  46. Capanni C, Cenni V, Mattioli E et al (2003) Failure of lamin A/C to functionally assemble in R482L mutated familial partial lipodystrophy fibroblasts: altered intermolecular interaction with emerin and implications for gene transcription. Exp Cell Res 291:122–134.

    Article  PubMed  CAS  Google Scholar 

  47. Caux F, Dubosclard E, Lascols O et al (2003) A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy. J Clin Endocrinol Metab 88:1006–1013

    Article  PubMed  CAS  Google Scholar 

  48. Csoka AB, Cao H, Sammak PJ et al (2004) Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes. J Med Genet 41:304–308

    Article  PubMed  CAS  Google Scholar 

  49. Young J, Morbois-Trabut L, Couzinet B et al (2005) Type A insulin resistance syndrome revealing a novel lamin A mutation. Diabetes 54:1873–1878

    Article  PubMed  CAS  Google Scholar 

  50. Goizet C, Yaou RB, Demay L et al (2004) A new mutation of the lamin A/C gene leading to autosomal dominant axonal neuropathy, muscular dystrophy, cardiac disease, and leuconychia. J Med Genet 41:e29

    Article  PubMed  CAS  Google Scholar 

  51. Benedetti S, Bertini E, Iannaccone S et al (2005) Dominant LMNA mutations can cause combined muscular dystrophy and peripheral neuropathy. J Neurol Neurosurg Psychiatry 76:1019–1021

    Article  PubMed  CAS  Google Scholar 

  52. Padiath QS, Fu YH (2010) Autosomal dominant leukodystrophy caused by lamin B1 duplications a clinical and molecular case study of altered nuclear function and disease. Methods Cell Biol 98:337–357

    Article  PubMed  CAS  Google Scholar 

  53. Dominguez-Gerpe L, Araujo-Vilar D (2008) Prematurely aged children: molecular alterations leading to Hutchinson-Gilford progeria and Werner syndromes. Curr Aging Sci 1:202–212

    Article  PubMed  CAS  Google Scholar 

  54. Columbaro M, Capanni C, Mattioli E et al (2005) Rescue of heterochromatin organization in Hutchinson-Gilford progeria by drug treatment. Cell Mol Life Sci 62:2669–2678

    Article  PubMed  CAS  Google Scholar 

  55. Cunningham VJ, D’Apice MR, Licata N et al (2010) Skeletal phenotype of mandibuloacral dysplasia associated with mutations in ZMPSTE24. Bone 47:591–597

    Article  PubMed  CAS  Google Scholar 

  56. Simha V, Agarwal AK, Oral EA et al (2003) Genetic and phenotypic heterogeneity in patients with mandibuloacral dysplasia-associated lipodystrophy. J Clin Endocrinol Metab 88:2821–2824

    Article  PubMed  CAS  Google Scholar 

  57. Agarwal AK, Fryns JP, Auchus RJ et al (2003) Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia. Hum Mol Genet 12:1995–2001

    Article  PubMed  CAS  Google Scholar 

  58. Filesi I, Gullotta F, Lattanzi G et al (2005) Alterations of nuclear envelope and chromatin organization in mandibuloacral dysplasia, a rare form of laminopathy. Physiol Genomics 23:150–158

    Article  PubMed  CAS  Google Scholar 

  59. Maraldi NM, Lattanzi G (2007) Involvement of prelamin A in laminopathies. Crit Rev Eukaryot Gene Expr 17:317–334

    Article  PubMed  CAS  Google Scholar 

  60. Shumaker DK, Dechat T, Kohlmaier A et al (2006) Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci U S A 103:8703–8708

    Article  PubMed  CAS  Google Scholar 

  61. Navarro CL, De Sandre-Giovannoli A, Bernard R et al (2004) Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Hum Mol Genet 13:2493–2503

    Article  PubMed  CAS  Google Scholar 

  62. Moulson CL, Go G, Gardner JM et al (2005) Homozygous and compound heterozygous mutations in ZMPSTE24 cause the laminopathy restrictive dermopathy. J Invest Dermatol 125:913–919

    Article  PubMed  CAS  Google Scholar 

  63. Columbaro M, Mattioli E, Schena E et al (2010) Prelamin A processing and functional effects in restrictive dermopathy. Cell Cycle 9:4766–4768

    Article  PubMed  CAS  Google Scholar 

  64. Muchir A, van Engelen BG, Lammens M et al (2003) Nuclear envelope alterations in fibroblasts from LGMD1B patients carrying nonsense Y259X heterozygous or homozygous mutation in lamin A/C gene. Exp Cell Res 291:352–362

    Article  PubMed  CAS  Google Scholar 

  65. Van Der Kooi AJ, Bonne G, Eymard B et al (2002) Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy. Neurology 59:620–623

    Article  PubMed  CAS  Google Scholar 

  66. Kirschner J, Brune T, Wehnert M et al (2005) p.S143F mutation in lamin A/C: a new phenotype combining myopathy and progeria. Ann Neurol 57:148–151

    Article  PubMed  CAS  Google Scholar 

  67. Sabatelli P, Squarzoni S, Petrini S et al (1998) Oral exfoliative cytology for the non-invasive diagnosis in X-linked Emery-Dreifuss muscular dystrophy patients and carriers. Neuromuscul Disord 8:67–71

    Article  PubMed  CAS  Google Scholar 

  68. Wheeler MA, Warley A, Roberts RG et al (2010) Identification of an emerin-beta-catenin complex in the heart important for intercalated disc architecture and beta-catenin localisation. Cell Mol Life Sci 67:781–796

    Article  PubMed  CAS  Google Scholar 

  69. Ognibene A, Sabatelli P, Petrini S et al (1999) Nuclear changes in a case of X-linked Emery-Dreifuss muscular dystrophy. Muscle Nerve 22:864–869

    Article  PubMed  CAS  Google Scholar 

  70. Maraldi NM, Lattanzi G, Capanni C et al (2006) Laminopathies: a chromatin affair. Adv Enzyme Regul 46:33–49

    Article  PubMed  CAS  Google Scholar 

  71. Zhang Q, Bethmann C, Worth NF et al (2007) Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Hum Mol Genet 16:2816–2833

    Article  PubMed  CAS  Google Scholar 

  72. Wilson KL, Berk JM (2010) The nuclear envelope at a glance. J Cell Sci 123:1973–1978

    Article  PubMed  CAS  Google Scholar 

  73. Zhang J, Felder A, Liu Y et al (2010) Nesprin 1 is critical for nuclear positioning and anchorage. Hum Mol Genet 19:329–341

    Article  PubMed  CAS  Google Scholar 

  74. Hoffmann K, Dreger CK, Olins AL et al (2002) Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger-Huet anomaly). Nat Genet 31:410–414

    PubMed  CAS  Google Scholar 

  75. Cohen TV, Klarmann KD, Sakchaisri K et al (2008) The lamin B receptor under transcriptional control of C/EBPepsilon is required for morphological but not functional maturation of neutrophils. Hum Mol Genet 17:2921–2933

    Article  PubMed  CAS  Google Scholar 

  76. Waterham HR, Koster J, Mooyer P et al (2003) Autosomal recessive HEM/Greenberg skeletal dysplasia is caused by 3 beta-hydroxysterol delta 14-reductase deficiency due to mutations in the lamin B receptor gene. Am J Hum Genet 72:1013–1017

    Article  PubMed  CAS  Google Scholar 

  77. Hellemans J, Preobrazhenska O, Willaert A et al (2004) Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Nat Genet 36:1213–1218

    Article  PubMed  CAS  Google Scholar 

  78. Puente XS, Quesada V, Osorio FG et al (2011) Exome sequencing and functional analysis identifies BANF1 mutation as the cause of a hereditary progeroid syndrome. Am J Hum Genet 88:650–656

    Article  PubMed  CAS  Google Scholar 

  79. Capanni C, Cenni V, Haraguchi T et al (2010) Lamin A precursor induces barrier-to- 989 autointegration factor nuclear localization. Cell Cycle 9:2600–2610

    Article  PubMed  CAS  Google Scholar 

  80. Kim CE, Perez A, Perkins G et al (2010) A molecular mechanism underlying the neural-specific defect in torsinA mutant mice. Proc Natl Acad Sci U S A 107:9861–9866

    Article  PubMed  CAS  Google Scholar 

  81. Hewett J, Gonzalez-Agosti C, Slater D et al (2000) Mutant torsinA, responsible for early-onset torsion dystonia, forms membrane inclusions in cultured neural cells. Hum Mol Genet 9:1403–1413

    Article  PubMed  CAS  Google Scholar 

  82. Nery FC, Zeng J, Niland BP et al (2008) TorsinA binds the KASH domain of nesprins and participates in linkage between nuclear envelope and cytoskeleton. J Cell Sci 121:3476–3486

    Article  PubMed  CAS  Google Scholar 

  83. Burke B, Roux KJ (2009) Nuclei take a position: managing nuclear location. Dev Cell 17:587–597

    Article  PubMed  CAS  Google Scholar 

  84. Szeverenyi I, Cassidy AJ, Chung CW et al (2008) The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases. Hum Mutat 29:351–360

    Article  PubMed  CAS  Google Scholar 

  85. Benedetti S, Menditto I, Degano M et al (2007) Phenotypic clustering of lamin A/C mutations in neuromuscular patients. Neurology 69:1285–1292

    Article  PubMed  CAS  Google Scholar 

  86. Lattanzi G, Cenni V, Marmiroli S et al (2003) Association of emerin with nuclear and cytoplasmic actin is regulated in differentiating myoblasts. Biochem Biophys Res Commun 303:764–770

    Article  PubMed  CAS  Google Scholar 

  87. Gueneau L, Bertrand AT, Jais JP et al (2009) Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy. Am J Hum Genet 85:338–353

    Article  PubMed  CAS  Google Scholar 

  88. Taylor MR, Slavov D, Gajewski A et al (2005) Thymopoietin (lamina-associated polypeptide 2) gene mutation associated with dilated cardiomyopathy. Hum Mutat 26:566–574

    Article  PubMed  CAS  Google Scholar 

  89. Naetar N, Korbei B, Kozlov S et al (2008) Loss of nucleoplasmic LAP2alpha-lamin A complexes causes erythroid and epidermal progenitor hyperproliferation. Nat Cell Biol 10:1341–1348

    Article  PubMed  CAS  Google Scholar 

  90. Shackleton S, Smallwood DT, Clayton P et al (2005) Compound heterozygous ZMPSTE24 mutations reduce prelamin a processing and result in a severe progeroid phenotype. J Med Genet 42:e36

    Article  PubMed  CAS  Google Scholar 

  91. Marmiroli S, Bertacchini J, Beretti F et al (2009) A-type lamins and signaling: the PI 3-kinase/Akt pathway moves forward. J Cell Physiol 220:553–561

    Article  PubMed  CAS  Google Scholar 

  92. Heessen S, Fornerod M (2007) The inner nuclear envelope as a transcription factor resting place. EMBO Rep 8:914–919

    Article  PubMed  CAS  Google Scholar 

  93. Broers JL, Machiels BM, Kuijpers HJ et al (1997) A- and B-type lamins are differentially expressed in normal human tissues. Histochem Cell Biol 107:505–517

    Article  PubMed  CAS  Google Scholar 

  94. Constantinescu D, Gray HL, Sammak PJ et al (2006) Lamin A/C expression is a marker of mouse and human embryonic stem cell differentiation. Stem Cells 24:177–185

    Article  PubMed  CAS  Google Scholar 

  95. Takamori Y, Tamura Y, Kataoka Y et al (2007) Differential expression of nuclear lamin, the major component of nuclear lamina, during neurogenesis in two germinal regions of adult rat brain. Eur J Neurosci 25:1653–1662

    Article  PubMed  Google Scholar 

  96. Capanni C, Del Coco R, Mattioli E et al (2009) Emerin-prelamin A interplay in human fibroblasts. Biol Cell 101:541–554

    Article  PubMed  CAS  Google Scholar 

  97. Friedl P, Wolf K, Lammerding J (2010) Nuclear mechanics during cell migration. Curr Opin Cell Biol 23:55–64

    Article  PubMed  CAS  Google Scholar 

  98. Wiesel N, Mattout A, Melcer S et al (2008) Laminopathic mutations interfere with the assembly, localization, and dynamics of nuclear lamins. Proc Natl Acad Sci U S A 105:180–185.

    Article  PubMed  CAS  Google Scholar 

  99. Broers JL, Kuijpers HJ, Ostlund C et al (2005) Both lamin A and lamin C mutations cause lamina instability as well as loss of internal nuclear lamin organization. Exp Cell Res 304:582–592

    Article  PubMed  CAS  Google Scholar 

  100. Ostlund C, Bonne G, Schwartz K et al (2001) Properties of lamin A mutants found in Emery-Dreifuss muscular dystrophy, cardiomyopathy and Dunnigan-type partial lipodystrophy. J Cell Sci 114:4435–4445

    PubMed  CAS  Google Scholar 

  101. Lammerding J, Schulze PC, Takahashi T et al (2004) Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J Clin Invest 113:370–378

    PubMed  CAS  Google Scholar 

  102. Melcon G, Kozlov S, Cutler DA et al (2006) Loss of emerin at the nuclear envelope disrupts the Rb1/E2F and MyoD pathways during muscle regeneration. Hum Mol Genet 15:637–651

    Article  PubMed  CAS  Google Scholar 

  103. Caron M, Auclair M, Donadille B et al (2007) Human lipodystrophies linked to mutations in Atype lamins and to HIV protease inhibitor therapy are both associated with prelamin A accumulation, oxidative stress and premature cellular senescence. Cell Death Differ 14:1759–1767

    Article  PubMed  CAS  Google Scholar 

  104. Meaburn KJ, Cabuy E, Bonne G et al (2007) Primary laminopathy fibroblasts display altered genome organization and apoptosis. Aging Cell 6:139–153

    Article  PubMed  CAS  Google Scholar 

  105. Gonzalez-Suarez I, Redwood AB, Perkins SM et al (2009) Novel roles for A-type lamins in telomere biology and the DNA damage response pathway. EMBO J 28:2414–2427

    Article  PubMed  CAS  Google Scholar 

  106. Benson EK, Lee SW, Aaronson SA (2010) Role of progerin-induced telomere dysfunction in HGPS premature cellular senescence. J Cell Sci 123:2605–2612

    Article  PubMed  CAS  Google Scholar 

  107. Maraldi NM, Lattanzi G (2005) Linkage of lamins to fidelity of gene transcription. Crit Rev Eukaryot Gene Expr 15:277–294

    Article  PubMed  CAS  Google Scholar 

  108. Huang S, Risques RA, Martin GM et al (2008) Accelerated telomere shortening and replicative senescence in human fibroblasts overexpressing mutant and wild-type lamin A. Exp Cell Res 314:82–91

    Article  PubMed  CAS  Google Scholar 

  109. Zhang HS, Dean DC (2001) Rb-mediated chromatin structure regulation and transcriptional repression. Oncogene 20:3134–3138

    Article  PubMed  CAS  Google Scholar 

  110. Markiewicz E, Dechat T, Foisner R et al (2002) Lamin A/C binding protein LAP2alpha is required for nuclear anchorage of retinoblastoma protein. Mol Biol Cell 13:4401–4413

    Article  PubMed  CAS  Google Scholar 

  111. Kotake Y, Cao R, Viatour P et al (2007) pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4alpha tumor suppressor gene. Genes Dev 21:49–54

    Article  PubMed  CAS  Google Scholar 

  112. Starr DA (2009) A nuclear-envelope bridge positions nuclei and moves chromosomes. J Cell Sci 122:577–586

    Article  PubMed  CAS  Google Scholar 

  113. Padmakumar VC, Libotte T, Lu W et al (2005) The inner nuclear membrane protein Sun1 mediates the anchorage of Nesprin-2 to the nuclear envelope. J Cell Sci 118:3419–3430

    Article  PubMed  CAS  Google Scholar 

  114. Haque F, Lloyd DJ, Smallwood DT et al (2006) SUN1 interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton. Mol Cell Biol 26:3738–3751

    Article  PubMed  CAS  Google Scholar 

  115. Lei K, Zhang X, Ding X et al (2009) SUN1 and SUN2 play critical but partially redundant roles in anchoring nuclei in skeletal muscle cells in mice. Proc Natl Acad Sci U S A 106:10207–10212

    Article  PubMed  Google Scholar 

  116. Mattioli E, Columbaro M, Capanni C et al (2011) Prelamin A-mediated recruitment of SUN1 to the nuclear envelope directs nuclear positioning in human muscle. Cell Death Differ 18:1305–1315

    Article  PubMed  CAS  Google Scholar 

  117. Wheeler MA, Davies JD, Zhang Q et al (2007) Distinct functional domains in nesprin-1alpha and nesprin-2beta bind directly to emerin and both interactions are disrupted in X-linked Emery-Dreifuss muscular dystrophy. Exp Cell Res 313:2845–2857

    Article  PubMed  CAS  Google Scholar 

  118. Puckelwartz MJ, Kessler EJ, Kim G et al (2010) Nesprin-1 mutations in human and murine cardiomyopathy. J Mol Cell Cardiol 48:600–608

    Article  PubMed  CAS  Google Scholar 

  119. Maraldi NM, Capanni C, Del Coco R et al (2011) Muscular laminopathies: Role of prelamin A in early steps of muscle differentiation. Adv Enzyme Regul 51:246–256

    Article  PubMed  CAS  Google Scholar 

  120. Kandert S, Luke Y, Kleinhenz T et al (2007) Nesprin-2 giant safeguards nuclear envelope architecture in LMNA S143F progeria cells. Hum Mol Genet 16:2944–2959

    Article  PubMed  CAS  Google Scholar 

  121. Kennedy BK, Barbie DA, Classon M et al (2000) Nuclear organization of DNA replication in primary mammalian cells. Genes Dev 14:2855–2868

    Article  PubMed  CAS  Google Scholar 

  122. Moir RD, Yoon M, Khuon S et al (2000) Nuclear lamins A and B1: different pathways of assembly during nuclear envelope formation in living cells. J Cell Biol 151:1155–1168

    Article  PubMed  CAS  Google Scholar 

  123. Naetar N, Foisner R (2009) Lamin complexes in the nuclear interior control progenitor cell proliferation and tissue homeostasis. Cell Cycle 8:1488–1493

    Article  PubMed  CAS  Google Scholar 

  124. Naetar N, Hutter S, Dorner D et al (2007) LAP2alpha-binding protein LINT-25 is a novel chromatin-associated protein involved in cell cycle exit. J Cell Sci 120:737–747

    Article  PubMed  CAS  Google Scholar 

  125. Bakay M, Wang Z, Melcon G et al (2006) Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb-MyoD pathways in muscle regeneration. Brain 129:996–1013

    Article  PubMed  Google Scholar 

  126. Marji J, O’Donoghue SI, McClintock D et al (2010) Defective lamin A-Rb signaling in Hutchinson-Gilford Progeria Syndrome and reversal by farnesyltransferase inhibition. PLoS One 5:e11132

    Article  PubMed  CAS  Google Scholar 

  127. Viteri G, Chung YW, Stadtman ER (2010) Effect of progerin on the accumulation of oxidized proteins in fibroblasts from Hutchinson Gilford progeria patients. Mech Ageing Dev 131:2–8

    Article  PubMed  CAS  Google Scholar 

  128. Richards SA, Muter J, Ritchie P et al (2011) The accumulation of unrepairable DNA damage in laminopathy progeria fibroblasts is caused by ROS generation and is prevented by treatment with N-acetyl cysteine. Hum Mol Genet 20:3997–4004

    Article  PubMed  CAS  Google Scholar 

  129. Liu Y, Wang Y, Rusinol AE et al (2008) Involvement of xeroderma pigmentosum group A (XPA) in progeria arising from defective maturation of prelamin A. FASEB J 22:603–611

    Article  PubMed  CAS  Google Scholar 

  130. Liu B, Wang J, Chan KM et al (2005) Genomic instability in laminopathy-based premature aging. Nat Med 11:780–785

    Article  PubMed  CAS  Google Scholar 

  131. Manju K, Muralikrishna B, Parnaik VK (2006) Expression of disease-causing lamin A mutants impairs the formation of DNA repair foci. J Cell Sci 119:2704–2714

    Article  PubMed  CAS  Google Scholar 

  132. Liu Y, Rusinol A, Sinensky M et al (2006) DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A. J Cell Sci 119:4644–4649

    Article  PubMed  CAS  Google Scholar 

  133. Vousden KH, Lane DP (2009) p53 in health and disease. Nat Rev Mol Cell Biol 8:275–283

    Article  CAS  Google Scholar 

  134. Decker ML, Chavez E, Vulto I et al (2009) Telomere length in Hutchinson-Gilford progeria syndrome. Mech Ageing Dev 130:377–383

    Article  PubMed  CAS  Google Scholar 

  135. Raz V, Vermolen BJ, Garini Y et al (2008) The nuclear lamina promotes telomere aggregation and centromere peripheral localization during senescence of human mesenchymal stem cells. J Cell Sci 121:4018–4028

    Article  PubMed  CAS  Google Scholar 

  136. Kudlow BA, Stanfel MN, Burtner CR et al (2008) Suppression of proliferative defects associated with processing-defective lamin A mutants by hTERT or inactivation of p53. Mol Biol Cell 19:5238–5248

    Article  PubMed  CAS  Google Scholar 

  137. Wallis CV, Sheerin AN, Green MH et al (2004) Fibroblast clones from patients with Hutchinson-Gilford progeria can senesce despite the presence of telomerase. Exp Gerontol 39:461–467

    Article  PubMed  CAS  Google Scholar 

  138. Du X, Shen J, Kugan N et al (2004) Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes. Mol Cell Biol 24:8437–8446

    Article  PubMed  CAS  Google Scholar 

  139. Moreau F, Boullu-Sanchis S, Vigouroux C et al (2007) Efficacy of pioglitazone in familial partial lipodystrophy of the Dunnigan type: a case report. Diabetes Metab 33:385–389

    Article  PubMed  CAS  Google Scholar 

  140. Gambineri A, Semple RK, Forlani G et al (2008) Monogenic polycystic ovary syndrome due to a mutation in the lamin A/C gene is sensitive to thiazolidinediones but not to metformin. Eur J Endocrinol 159:347–353

    Article  PubMed  CAS  Google Scholar 

  141. Gotic I, Schmidt WM, Biadasiewicz K et al (2010) Loss of LAP2 alpha delays satellite cell differentiation and affects postnatal fiber-type determination. Stem Cells 28:480–488

    Article  PubMed  CAS  Google Scholar 

  142. Parnaik VK, Manju K (2006) Laminopathies: multiple disorders arising from defects in nuclear architecture. J Biosci 31:405–421

    Article  PubMed  CAS  Google Scholar 

  143. Gotic I, Leschnik M, Kolm U et al (2010) Lamina-associated polypeptide 2alpha loss impairs heart function and stress response in mice. Circ Res 106:346–353

    Article  PubMed  CAS  Google Scholar 

  144. Worman HJ (2006) Inner nuclear membrane and regulation of Smad-mediated signaling. Biochim Biophys Acta 1761:626–631

    Article  PubMed  CAS  Google Scholar 

  145. Van Berlo JH, Voncken JW, Kubben N et al (2005) A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors. Hum Mol Genet 14:2839–2849

    Article  PubMed  CAS  Google Scholar 

  146. Arimura T, Helbling-Leclerc A, Massart C et al (2005) Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies. Hum Mol Genet 14:155–169

    Article  PubMed  CAS  Google Scholar 

  147. Muchir A, Shan J, Bonne G et al (2009) Inhibition of extracellular signal-regulated kinase signaling to prevent cardiomyopathy caused by mutation in the gene encoding A-type lamins. Hum Mol Genet 18:241–247

    Article  PubMed  CAS  Google Scholar 

  148. Favreau C, Delbarre E, Courvalin JC et al (2008) Differentiation of C2C12 myoblasts expressing lamin A mutated at a site responsible for Emery-Dreifuss muscular dystrophy is improved by inhibition of the MEK-ERK pathway and stimulation of the PI3-kinase pathway. Exp Cell Res 314:1392–1405

    Article  PubMed  CAS  Google Scholar 

  149. Muchir A, Pavlidis P, Decostre V et al (2007) Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy. J Clin Invest 117:1282–1293

    Article  PubMed  CAS  Google Scholar 

  150. Lin F, Morrison JM, Wu W, Worman HJ (2005) MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signaling. Hum Mol Genet 14(3):437–45 (Epub 2004 Dec 15)

    Article  PubMed  CAS  Google Scholar 

  151. González JM, Navarro-Puche A, Casar B et al(2008) Fast regulation of AP-1 activity through interaction of lamin A/C, ERK1/2, and c-Fos at the nuclear envelope. J Cell Biol 183:653–666

    Article  PubMed  CAS  Google Scholar 

  152. Ugalde AP, Ramsay AJ, de la Rosa J et al (2011) Aging and chronic DNA damage response activate a regulatory pathway involving miR-29 and p53. EMBO J 30:2219–2232

    Article  PubMed  CAS  Google Scholar 

  153. Scaffidi P, Misteli T (2008) Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing. Nat Cell Biol 10:452–459

    Article  PubMed  CAS  Google Scholar 

  154. Liu GH, Barkho BZ, Ruiz S, Diep D, Qu J, Yang SL, Panopoulos AD, Suzuki K, Kurian L, Walsh C, Thompson J, Boue S, Fung HL, Sancho-Martinez I, Zhang K (2011) Yates J 3rd, Izpisua Belmonte JC.Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature 472:221–225

    Article  PubMed  CAS  Google Scholar 

  155. Pekovic V, Hutchison CJ (2008) Adult stem cell maintenance and tissue regeneration in the ageing context: the role for A-type lamins as intrinsic modulators of ageing in adult stem cells and their niches. J Anat 213:5–25

    Article  PubMed  CAS  Google Scholar 

  156. Markiewicz E, Tilgner K, Barker N et al (2006) The inner nuclear membrane protein emerin regulates beta-catenin activity by restricting its accumulation in the nucleus. EMBO J 25:3275–3285

    Article  PubMed  CAS  Google Scholar 

  157. Hernandez L, Roux KJ, Wong ES et al (2010) Functional coupling between the extracellular matrix and nuclear lamina by Wnt signaling in progeria. Dev Cell 19:413–425

    Article  PubMed  CAS  Google Scholar 

  158. Mariño G, Ugalde AP, Fernández AF et al (2010) Insulin-like growth factor 1 treatment extends longevity in a mouse model of human premature aging by restoring somatotroph axis function. Proc Natl Acad Sci U S A 107:16268–16273

    Article  PubMed  Google Scholar 

  159. Dechat T, Pfleghaar K, Sengupta K et al (2008) Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes Dev 22:832–853

    Article  PubMed  CAS  Google Scholar 

  160. McNally EM (2007) New approaches in the therapy of cardiomyopathy in muscular dystrophy. Annu Rev Med 58:75–88

    Article  PubMed  CAS  Google Scholar 

  161. Capeau J, Magre J, Caron-Debarle M et al (2010) Human lipodystrophies: genetic and acquired diseases of adipose tissue. Endocr Dev 19:1–20

    Article  PubMed  CAS  Google Scholar 

  162. de Pablos-Velasco P (2010) Pioglitazone: beyond glucose control. Expert Rev Cardiovasc Ther 8:1057–1067

    Article  PubMed  CAS  Google Scholar 

  163. Varela I, Pereira S, Ugalde AP et al (2008) Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging. Nat Med 14:767–772

    Article  PubMed  CAS  Google Scholar 

  164. Osorio FG, Navarro CL, Cadiñanos J et al (2011) Splicing-directed therapy in a new mouse model of human accelerated aging. Sci Transl Med 3:106–107

    Article  CAS  Google Scholar 

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Acknowledgments

The authors wish to thank Marta Columbaro and Cristina Capanni for revising the manuscript and for the helpful discussion. This work was supported by: A. I. Pro. Sa. B., Italy; EU-funded FP6 Euro-Laminopathies project; Italian MIUR PRIN 2008 to G. L. and N. M. M.; ISS Rare Diseases Italy–U. S. A. program (grant number 526/D30); Fondazione Carisbo, Italy, FIRB-MIUR Grant 2010 to N. M. M.

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Authors and Affiliations

  1. Laboratory of Musculoskeletal Cell Biology, Rizzoli Orthopedic Institute, Via di Barbiano 1/10, 40136, Bologna, Italy

    Nadir M. Maraldi

  2. Department of Anatomical Sciences, University of Bologna, Bologna, Italy

    Nadir M. Maraldi

  3. National Research Council of Italy CNR-IOR, Institute of Molecular Genetics, Unit of Bologna, Bologna, Italy

    Giovanna Lattanzi

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  1. Nadir M. Maraldi
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Correspondence to Nadir M. Maraldi .

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  1. Australia for Medical Research, Iron Metabolism Program, Children's Cancer Institute, Randwick, New South Wales, Australia

    Maria Kavallaris

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Maraldi, N.M., Lattanzi, G. (2012). Laminopathies. In: Kavallaris, M. (eds) Cytoskeleton and Human Disease. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-788-0_18

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