The laminopathies: Nuclear structure meets disease

Current Opinion in Genetics and Development

Volumn 13, Issue 3, 2003, Pages 223-230

  Mounkes, Leslie ^a   Kozlov, Serguei ^a   Burke, Brian ^b   Stewart, Colin L ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b UNIVERSITY OF FLORIDA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LAMIN A;

CELL NUCLEUS MEMBRANE; DISEASE ASSOCIATION; DISEASE COURSE; GENE MUTATION; GENETIC CODE; GENETIC DISORDER; HUMAN; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; TISSUE SPECIFICITY;

EID: 0037674654     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(03)00058-3     Document Type: Review

References (63)

1. Macara I.G. Transport into and out of the nucleus. Microbiol. Mol. Biol. Rev. 65:2001;570-594.
2. Gerace L., Burke B. Functional organization of the nuclear envelope. Annu. Rev. Cell Biol. 4:1988;335-374.
3. Stuurman N., Heins S., Aebi U. Nuclear lamins: their structure, assembly, and interactions. J. Struct. Biol. 122:1998;42-66.
4. Moir R.D., Spann T.P., Lopez-Soler R.I., Yoon M., Goldman A.E., Khuon S., Goldman R.D. The dynamics of the nuclear lamins during the cell cycle-relationship between structure and function. J. Struct. Biol. 129:2000;324-334.
5. Alsheimer M., Benavente R. Change of karyoskeleton during mammalian spermatogenesis: expression pattern of nuclear lamin C2 and its regulation. Exp. Cell Res. 228:1996;181-188.
6. Holtz D., Tanaka R.A., Hartwig J., McKeon F. The CaaX Motif of lamin A functions in conjunction with the nuclear localization signal to target assembly to the nuclear envelope. Cell. 59:1989;969-977.
7. Kitten G.T., Nigg E.A. The CaaX motif is required for isoprenylation, carboxy methylation and nuclear membrane association of lamin B2. J. Cell Biol. 113:1991;13-24.
8. •].
9. •] show that some mice lacking the proteolytic enzyme Zmpste24, which processes farnesylated proteins, develop DCM, muscular dystrophy, lipodystrophy, defective bone repair and often die prematurely, with some of these pathologies common to the lamin-deficient mice. The mice have defective postranslational processing of lamin A, revealing another mechanism underlying the development of the different laminopathies.
10. Stewart C., Burke B. Teratocarcinoma stem cells and early mouse embryos contain only a single major lamin polypeptide closely resembling lamin B. Cell. 51:1987;383-392.
11. Roeber R.-A., Sauter H., Weber K., Osborn M. Cells of the cellular immune and hemopoietic system of the mouse lack lamins A/C: distinction versus other somatic cells. J. Cell Sci. 95:1990;587-598.
12. Broers J.L., Machiels B.M., Kuijpers H.J., Smedts F., van den Kieboom R., Raymond Y., Ramaekers F.C. A- and B-type lamins are differentially expressed in normal human tissues. Histochem. Cell Biol. 107:1997;505-517.
13. Sullivan T., Escalante-Alcalde D., Bhatt H., Anver M., Bhat N., Nagashima K., Stewart C.L., Burke B. Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J. Cell Biol. 147:1999;913-920.
14. Burke B., Stewart C.L. Life at the edge: the nuclear envelope and human disease. Nat. Rev. Mol. Cell Biol. 3:2002;575-585.
15. Bannister A.J., Zegerman P., Partridge J.F., Miska E.A., Thomas J.O., Allshire R.C., Kouzarides T. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature. 410:2001;120-124.
16. Lachner M., O'Carroll D., Rea S., Mechtler K., Jenuwein T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature. 410:2001;116-120.
17. Laguri C., Gilquin B., Wolff N., Romi-Lebrun R., Courchay K., Callebaut I., Worman H.J., Zinn-Justin S. Structural characterization of the LEM motif common to three human inner nuclear membrane proteins. Structure. 9:2001;503-511.
18. Shumaker D.K., Lee K.K., Tanhehco Y.C., Craigie R., Wilson K.L. LAP2 binds to BAF.DNA complexes: requirement for the LEM domain and modulation by variable regions. EMBO J. 20:2001;1754-1764.
19. Zheng R., Ghirlando R., Lee M.S., Mizuuchi K., Krause M., Craigie R. Barrier-to-autointegration factor (BAF) bridges DNA in a discrete, higher-order nucleoprotein complex. Proc. Natl. Acad. Sci. U.S.A. 97:2000;8997-9002.
20. Glass C.A., Glass J.R., Taniura H., Hasel K.W., Blevitt J.M., Gerace L. The alpha-helical rod domain of human lamins A and C contains a chromatin binding site. EMBO J. 12:1993;4413-4424.
21. Nili E., Cojocaru G.S., Kalma Y., Ginsberg D., Copeland N.G., Gilbert D.J., Jenkins N.A., Berger R., Shaklai S., Amariglio N.et al. Nuclear membrane protein LAP2beta mediates transcriptional repression alone and together with its binding partner GCL (germ-cell-less). J. Cell Sci. 114:2001;3297-3307.
22. Holaska J.M., Lee K.K., Kowalski A.K., Wilson K.L. Transcriptional repressor germ cell-less (GCL) and barrier-to-autointegration factor (BAF) compete for binding to emerin in vitro. J. Biol. Chem. 278:2002;6969-6975.
23. Kimura T., Ito C., Watanabe S., Takahashi T., Ikawa M., Yomogida K., Fujita Y., Ikeuchi M., Asada N., Matsumiya K.et al. Mouse germ cell-less as an essential component for nuclear integrity. Mol. Cell Biol. 23:2003;1304-1315 This paper shows that disruption of the transcriptional co-factor Gcl, which is associated with the NE, leads to both cellular defects and alterations to the NE. Gcl may, therefore, be one of the proteins whose localization is dependent on the lamins and is important to NE organization.
24. Bione S., Maestrini E., Rivella S., Mancini M., Regis S., Romeo G., Toniolo D. Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy. Nat. Genet. 8:1994;323-327.
25. Emery A.E. Emery-Dreifuss muscular dystrophy and other related disorders. Br. Med. Bull. 45:1989;772-787.
26. Fairley E.A., Kendrick-Jones J., Ellis J.A. The Emery-Dreifuss muscular dystrophy phenotype arises from aberrant targeting and binding of emerin at the inner nuclear membrane. J. Cell Sci. 112:1999;2571-2582.
27. •].
28. •] show that mutations in the gene for LBR, which is associated with the NE and binds to the heterochromatic factor HP1, result in developmental pathologies. They further reveal the importance of the NE in regulating gene expression and in the development of disease.
29. Bonne G., Di Barletta M.R., Varnous S., Becane H.M., Hammouda E.H., Merlini L., Muntoni F., Greenberg C.R., Gary F., Urtizberea J.A.et al. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery- Dreifuss muscular dystrophy. Nat. Genet. 21:1999;285-288.
30. Muchir A., Bonne G., van der Kooi A.J., van Meegen M., Baas F., Bolhuis P.A., de Visser M., Schwartz K. 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. 9:2000;1453-1459.
31. Fatkin D., MacRae C., Sasaki T., Wolff M.R., Porcu M., Frenneaux M., Atherton J., Vidaillet H.J. Jr., Spudich S., De Girolami U.et al. 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. 341:1999;1715-1724.
32. Cao H., Hegele R.A. Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan- type familial partial lipodystrophy. Hum. Mol. Genet. 9:2000;109-112.
33. Novelli G., Muchir A., Sangiuolo F., Helbling-Leclerc A., D'Apice M.R., Massart C., Capon F., Sbraccia P., Federici M., Lauro R.et al. Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. Am. J. Hum. Genet. 71:2002;426-431.
34. De Sandre-Giovannoli A., Chaouch M., Kozlov S., Vallat J.M., Tazir M., Kassouri N., Szepetowski P., Hammadouche T., Vandenberghe A., Stewart C.L.et al. 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. 70:2002;726-736.
35. Brodsky G.L., Muntoni F., Miocic S., Sinagra G., Sewry C., Mestroni L. Lamin A/C gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement. Circulation. 101:2000;473-476 The same mutation in one family results in three of the affected individuals each developing a clinically different striated muscle pathology. This demonstrates the often great variability seen in the laminopathies and how a disease associated with a particular mutation progresses, suggesting that other, as yet unidentified factors, are important influences on the outcome of the disease.
36. Wehnert M.S., Bonne G. The nuclear muscular dystrophies. Semin. Pediatr. Neurol. 9:2002;100-107.
37. Vigouroux C., Magre J., Vantyghem M.C., Bourut C., Lascols O., Shackleton S., Lloyd D.J., Guerci B., Padova G., Valensi P.et al. Lamin A/C gene: sex-determined expression of mutations in Dunnigan-type familial partial lipodystrophy and absence of coding mutations in congenital and acquired generalized lipoatrophy. Diabetes. 49:2000;1958-1962.
38. Simha V., Garg A. Body fat distribution and metabolic derangements in patients with familial partial lipodystrophy associated with mandibuloacral dysplasia. J. Clin. Endocrinol. Metab. 87:2002;776-785.
39. Garg A., Speckman R.A., Bowcock A.M. Multisystem dystrophy syndrome due to novel missense mutations in the amino-terminal head and alpha-helical rod domains of the lamin A/C gene. Am. J. Med. 112:2002;549-555.
40. Cutler D.A., Sullivan T., Marcus-Samuels B., Stewart C.L., Reitman M.L. Characterization of adiposity and metabolism in Lmna-deficient mice. Biochem. Biophys. Res. Commun. 291:2002;522-527.
41. Raharjo W.H., Enarson P., Sullivan T., Stewart C.L., Burke B. Nuclear envelope defects associated with LMNA mutations cause dilated cardiomyopathy and Emery-Dreifuss muscular dystrophy. J. Cell Sci. 114:2001;4447-4457.
42. Maniotis A.J., Chen C.S., Ingber D.E. Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc. Natl. Acad. Sci. U.S.A. 94:1997;849-854.
43. De Keulenaer G.W., Wang Y., Feng Y., Muangman S., Yamamoto K., Thompson J.F., Turi T.G., Landschutz K., Lee R.T. Identification of IEX-1 as a biomechanically controlled nuclear factor-κB target gene that inhibits cardiomyocyte hypertrophy. Circ. Res. 90:2002;690-696.
44. Vallee R.B., Tai C., Faulkner N.E. LIS1: cellular function of a disease-causing gene. Trends Cell Biol. 11:2001;155-160.
45. Xiang X., Osmani A.H., Osmani S.A., Xin M., Morris N.R. NudF, a nuclear migration gene in Aspergillus nidulans, is similar to the human LIS-1 gene required for neuronal migration. Mol. Biol. Cell. 6:1995;297-310.
46. Malone C.J., Fixsen W.D., Horvitz H.R., Han M. UNC-84 localizes to the nuclear envelope and is required for nuclear migration and anchoring during C. elegans development. Development. 126:1999;3171-3181.
47. Starr D.A., Hermann G.J., Malone C.J., Fixsen W., Priess J.R., Horvitz H.R., Han M. unc-83 encodes a novel component of the nuclear envelope and is essential for proper nuclear migration. Development. 128:2001;5039-5050.
48. Guillemin K., Williams T., Krasnow M.A. A nuclear lamin is required for cytoplasmic organization and egg polarity in Drosophila. Nat. Cell Biol. 3:2001;848-851 This paper shows that the NE is important in determining migration of the nucleus during branching morphogenesis, in the subcellular localization and function of Gurken mRNA that is important for oocyte polarity.
49. Apel E.D., Lewis R.M., Grady R.M., Sanes J.R. Syne-1, a dystrophin- and Klarsicht-related protein associated with synaptic nuclei at the neuromuscular junction. J. Biol. Chem. 275:2000;31986-31995.
50. Mislow J.M., Kim M.S., Davis D.B., McNally E.M. Myne-1, a spectrin repeat transmembrane protein of the myocyte inner nuclear membrane, interacts with lamin A/C. J. Cell Sci. 115:2002;61-70.
51. Zhang Q., Ragnauth C., Greener M.J., Shanahan C.M., Roberts R.G. The nesprins are giant actin-binding proteins, orthologous to Drosophila melanogaster muscle protein MSP-300. Genomics. 80:2002;473-481.
52. Mislow J.M., Holaska J.M., Kim M.S., Lee K.K., Segura-Totten M., Wilson K.L., McNally E.M. Nesprin-1α self-associates and binds directly to emerin and lamin A in vitro. FEBS Lett. 525:2002;135-140.
53. Starr D.A., Han M. Role of ANC-1 in tethering nuclei to the actin cytoskeleton. Science. 298:2002;406-409 This paper shows that the C. elegans protein, Anc-1, which is the orthologue of the mammalian Nesprins, is a factor that tethers the NE to the cytoskeletal actin network, providing a molecular basis as to how the nucleus is positioned within the cell. The function of Anc-1 is dependent on the C. elegans lamin.
54. Lee K.K., Starr D., Cohen M., Liu J., Han M., Wilson K.L., Gruenbaum Y. Lamin-dependent localization of UNC-84, a protein required for nuclear migration in Caenorhabditis elegans. Mol. Biol. Cell. 13:2002;892-901.
55. Cockell M., Gasser S.M. Nuclear compartments and gene regulation. Curr. Opin. Genet. Dev. 9:1999;199-205.
56. Ostlund C., Bonne G., Schwartz K., Worman H.J. Properties of lamin A mutants found in Emery-Dreifuss muscular dystrophy, cardiomyopathy and Dunnigan-type partial lipodystrophy. J. Cell Sci. 114:2001;4435-4445.
57. ••].
58. ••] describe the structure of the Lamin A carboxyl terminus globular domain and suggest a molecular basis to how different pathologies may arise from the different mutations within the LMNA gene.
59. Lloyd D.J., Trembath R.C., Shackleton S. A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies. Hum. Mol. Genet. 11:2002;769-777.
60. Wilson K.L. The nuclear envelope, muscular dystrophy and gene expression. Trends Cell Biol. 10:2000;125-129.
61. De Sandre-Giovannoli A, Bernard R, Cau P, Navarro C, Amiel J, Boccaccio I, Lyonnet S, Stewart CL, Munnich A, Le Merrer M, Lévy N: Lamin A truncation in Hutchinson-Gilford Progeria. Science 2003, in press.
62. Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P et al.: Recurrent de novo point mutations in Lamin A cause Hutchinson-Gilford Progeria syndrome. Nature 2003, in press.
63. Mounkes LC, Kozlov S, Hernandez L, Sullivan T, Stewart CL: A Progeroid syndrome in mice is caused by defects in the A-type lamins. Nature 2003, in press.