Lamins and lamin-associated proteins in aging and disease

Current Opinion in Cell Biology

Volumn 19, Issue 3, 2007, Pages 298-304

  Vlcek, Sylvia ^a   Foisner, Roland ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

EMERIN; LAMIN; LAMIN A; LAMIN B; LAMIN B RECEPTOR; LAMINA ASSOCIATED POLYPEPTIDE 2; NUCLEAR PROTEIN; STRUCTURAL PROTEIN; SUN DOMAIN PROTEIN; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

AGING; CELL CYCLE REGULATION; CELL DIFFERENTIATION; CELL NUCLEUS MEMBRANE; CHROMATIN; DISEASE ACTIVITY; DNA REPAIR; GENOMIC INSTABILITY; HETEROCHROMATIN; HUMAN; MECHANICAL STRESS; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; RETINOBLASTOMA; REVIEW; SCAVENGING SYSTEM; STEM CELL; STRESS;

AGING; ANIMALS; CELL NUCLEUS; CHROMATIN; DISEASE; HUMANS; LAMINS; MODELS, BIOLOGICAL; SIGNAL TRANSDUCTION;

EID: 34250166469     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ceb.2007.04.001     Document Type: Review

References (53)

1. Burke B., and Stewart C.L. The laminopathies: the functional architecture of the nucleus and its contribution to disease. Annu Rev Genomics Hum Genet 7 (2006) 369-405
2. Vlcek S., and Foisner R. A-type lamin networks in light of laminopathic diseases. Biochim Biophys Acta (2006)
3. Fong L.G., Ng J.K., Lammerding J., Vickers T.A., Meta M., Cote N., Gavino B., Qiao X., Chang S.Y., Young S.R., et al. Prelamin A and lamin A appear to be dispensable in the nuclear lamina. J Clin Invest 116 (2006) 743-752. The generation of a lamin C - only mouse that is entirely healthy and shows minimal nuclear abnormalities suggests that prelamin A and lamin A are dispensable in mice. This may enable new strategies for the treatment of laminopathies. However the transferability of these findings to humans remains to be shown.
4. Rusinol A.E., and Sinensky M.S. Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors. J Cell Sci 119 (2006) 3265-3272
5. King M.C., Lusk C.P., and Blobel G. Karyopherin-mediated import of integral inner nuclear membrane proteins. Nature 442 (2006) 1003-1007. This study shows that, at least in yeast some INM proteins require active, nuclear localization sequence-dependent pathways for correct targeting to the INM, similar to the nuclear transport of soluble nuclear proteins. This extends the previous diffusion/retention model, which suggested lateral passive diffusion of INM proteins within the endoplasmic reticulum/nuclear membrane layers and retention by specific interactions with nuclear structures. The structural details of the translocation of INM proteins across the NPCs remain to be solved.
6. Capell B.C., and Collins F.S. Human laminopathies: nuclei gone genetically awry. Nat Rev Genet 7 (2006) 940-952
7. Navarro C.L., Cau P., and Levy N. Molecular bases of progeroid syndromes. Hum Mol Genet 15 Spec No 2 (2006) R151-R161
8. •]
9. •] describes a potential involvement of lamins in the normal aging process. While the above study revealed a mutual link between nuclear integrity and life span in C. elegans, this manuscript describes the sporadic generation of a Hutchinson Gilford Progeria-linked prelamin A variant in humans that causes age related defects in old cells.
10. Hegele R.A., Cao H., Liu D.M., Costain G.A., Charlton-Menys V., Rodger N.W., and Durrington P.N. Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. Am J Hum Genet 79 (2006) 383-389
11. Padiath Q.S., Saigoh K., Schiffmann R., Asahara H., Yamada T., Koeppen A., Hogan K., Ptacek L.J., and Fu Y.H. Lamin B1 duplications cause autosomal dominant leukodystrophy. Nat Genet 38 (2006) 1114-1123
12. Gotzmann J., and Foisner R. A-type lamin complexes and regenerative potential: a step towards understanding laminopathic diseases?. Histochem Cell Biol 125 (2006) 33-41
13. Lammerding J., Schulze P.C., Takahashi T., Kozlov S., Sullivan T., Kamm R.D., Stewart C.L., and Lee R.T. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J Clin Invest 113 (2004) 370-378
14. Lammerding J., Hsiao J., Schulze P.C., Kozlov S., Stewart C.L., and Lee R.T. Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells. J Cell Biol 170 (2005) 781-791
15. Goldman R.D., Shumaker D.K., Erdos M.R., Eriksson M., Goldman A.E., Gordon L.B., Gruenbaum Y., Khuon S., Mendez M., Varga R., et al. Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci USA 101 (2004) 8963-8968
16. Scaffidi P., and Misteli T. Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome. Nat Med 11 (2005) 440-445. This is the first report on the rescue of the cellular phenotypes in HGPS cells by using antisense-oligonucleotides targeting the activated lamin A cryptic splice site in HGPS. This study also provided convincing evidence for a causal link between the accumulation of progerin and the disease phenotypes on the cellular level.
17. Dahl K.N., Scaffidi P., Islam M.F., Yodh A.G., Wilson K.L., and Misteli T. Distinct structural and mechanical properties of the nuclear lamina in Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci USA 103 (2006) 10271-10276
18. Delbarre E., Tramier M., Coppey-Moisan M., Gaillard C., Courvalin J.C., and Buendia B. The truncated prelamin A in Hutchinson-Gilford progeria syndrome alters segregation of A-type and B-type lamin homopolymers. Hum Mol Genet 15 (2006) 1113-1122
19. Padmakumar V.C., Libotte T., Lu W., Zaim H., Abraham S., Noegel A.A., Gotzmann J., Foisner R., and Karakesisoglou I. The inner nuclear membrane protein Sun1 mediates the anchorage of Nesprin-2 to the nuclear envelope. J Cell Sci 118 (2005) 3419-3430
20. Crisp M., Liu Q., Roux K., Rattner J.B., Shanahan C., Burke B., Stahl P.D., and Hodzic D. Coupling of the nucleus and cytoplasm: role of the LINC complex. J Cell Biol 172 (2006) 41-53
21. Haque F., Lloyd D.J., Smallwood D.T., Dent C.L., Shanahan C.M., Fry A.M., Trembath R.C., and Shackleton S. 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 (2006) 3738-3751
22. Starr D.A., and Fischer J.A. KASH 'n Karry: the KASH domain family of cargo-specific cytoskeletal adaptor proteins. Bioessays 27 (2005) 1136-1146
23. Wilhelmsen K., Litjens S.H., Kuikman I., Tshimbalanga N., Janssen H., van den Bout I., Raymond K., and Sonnenberg A. Nesprin-3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin. J Cell Biol 171 (2005) 799-810
24. Nikolova V., Leimena C., McMahon A.C., Tan J.C., Chandar S., Jogia D., Kesteven S.H., Michalicek J., Otway R., Verheyen F., et al. Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C-deficient mice. J Clin Invest 113 (2004) 357-369
25. Mattout A., Goldberg M., Tzur Y., Margalit A., and Gruenbaum Y. Specific and conserved sequences in D. melanogaster and C. elegans lamins and histone H2A mediate the attachment of lamins to chromosomes. J Cell Sci 120 (2007) 77-85. In vitro binding studies show that specific sequences in the C-terminal Ig fold of lamins and both histone 2A head and tail domains are essential for the interaction of lamins with chromatin. These studies provide further mechanistic insights into the potential role of lamins in chromatin organization and may help explain chromatin defects observed in laminopathic cells.
26. Pickersgill H., Kalverda B., de Wit E., Talhout W., Fornerod M., and van Steensel B. Characterization of the Drosophila melanogaster genome at the nuclear lamina. Nat Genet 38 (2006) 1005-1014. This study provides in vivo evidence for the role of lamins in the global organization and epigenetic control of transcriptionally silent chromatin at the nuclear periphery.
27. Somech R., Shaklai S., Geller O., Amariglio N., Simon A.J., Rechavi G., and Gal-Yam E.N. The nuclear-envelope protein and transcriptional repressor LAP2β interacts with HDAC3 at the nuclear periphery, and induces histone H4 deacetylation. J Cell Sci 118 (2005) 4017-4025
28. Makatsori D., Kourmouli N., Polioudaki H., Shultz L.D., McLean K., Theodoropoulos P.A., Singh P.B., and Georgatos S.D. The inner nuclear membrane protein lamin B receptor forms distinct microdomains and links epigenetically marked chromatin to the nuclear envelope. J Biol Chem 279 (2004) 25567-25573
29. Margalit A, Brachner A, Gotzmann J, Foisner R, Gruenbaum Y: Barrier to Autointegration factor - Baffling little protein. Trends Cell Biol 2007, in press.
30. Shumaker D.K., Dechat T., Kohlmaier A., Adam S.A., Bozovsky M.R., Erdos M.R., Eriksson M., Goldman A.E., Khuon S., Collins F.S., et al. Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci USA 103 (2006) 8703-8708. This report provides evidence for profound epigenetic changes and loss of heterochromatin in HGPS cells that may be relevant for the premature aging pathologies in HGPS patients and may also reflect certain aspects of normal aging.
31. Ivorra C., Kubicek M., Gonzalez J.M., Sanz-Gonzalez S.M., Alvarez-Barrientos A., O'Connor J.E., Burke B., and Andres V. A mechanism of AP-1 suppression through interaction of c-Fos with lamin A/C. Genes Dev 20 (2006) 307-320
32. Capanni C., Mattioli E., Columbaro M., Lucarelli E., Parnaik V.K., Novelli G., Wehnert M., Cenni V., Maraldi N.M., Squarzoni S., et al. Altered pre-lamin A processing is a common mechanism leading to lipodystrophy. Hum Mol Genet 14 (2005) 1489-1502
33. Boguslavsky R.L., Stewart C.L., and Worman H.J. Nuclear lamin A inhibits adipocyte differentiation: implications for Dunnigan-type familial partial lipodystrophy. Hum Mol Genet 15 (2006) 653-663
34. Worman H.J. Inner nuclear membrane and regulation of Smad-mediated signaling. Biochim Biophys Acta 1761 (2006) 626-631
35. Hellemans J., Preobrazhenska O., Willaert A., Debeer P., Verdonk P.C., Costa T., Janssens K., Menten B., Van Roy N., Vermeulen S.J., et al. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. Nat Genet 36 (2004) 1213-1218
36. Ishimura A., Ng J.K., Taira M., Young S.G., and Osada S. Man1, an inner nuclear membrane protein, regulates vascular remodeling by modulating transforming growth factor β signaling. Development 133 (2006) 3919-3928. This paper confirms an antagonistic role of the INM protein MAN1 in TGFß signaling in vivo during mouse development and reveals a novel crucial function of MAN1 in angiogenesis.
37. Holaska J.M., Rais-Bahrami S., and Wilson K.L. Lmo7 is an emerin-binding protein that regulates the transcription of emerin and many other muscle-relevant genes. Hum Mol Genet 15 (2006) 3459-3472
38. Markiewicz E., Tilgner K., Barker N., van de Wetering M., Clevers H., Dorobek M., Hausmanowa-Petrusewicz I., Ramaekers F.C., Broers J.L., Blankesteijn W.M., et al. The inner nuclear membrane protein emerin regulates beta-catenin activity by restricting its accumulation in the nucleus. EMBO J 25 (2006) 3275-3285. Using emerin-deficient fibroblasts from Emery Dreifuss muscular dystrophy patients, the authors provide evidence for an intriguing novel role of emerin in the regulation of the localization and transcriptional activity of β-catenin, which may be involved in the control of cell proliferation. Although the exact mechanisms remain unclear, these findings may be relevant for understanding some of the pathological phenotypes in laminopathy patients, such as increased fibrosis in heart and skeletal muscle caused by an accelerated turn over of fibroblasts.
39. Galderisi U., Cipollaro M., and Giordano A. The retinoblastoma gene is involved in multiple aspects of stem cell biology. Oncogene 25 (2006) 5250-5256
40. Dorner D., Vlcek S., Foeger N., Gajewski A., Makolm C., Gotzmann J., Hutchison C.J., and Foisner R. Lamina-associated polypeptide 2α regulates cell cycle progression and differentiation via the retinoblastoma-E2F pathway. J Cell Biol 173 (2006) 83-93. This manuscript reveals a novel role of nucleoplasmic lamin A/C-LAP2α complexes in the regulation of Rb function in cell cycle exit during differentiation. An impairment of this function causing a deregulation of adult stem cell activity in tissue regeneration may contribute to some of the pathological phenotypes in laminopathies.
41. Pekovic V, Harborth J, Broers JL, Ramaekers FC, van Engelen B, Lammens M, von Zglinicki T, Foisner R, Hutchison C, Markiewicz E: Nucleoplasmic LAP2alpha-lamin A complexes are required to maintain a proliferative state in human fibroblasts. J Cell Biol 2007, in press.
42. Johnson B.R., Nitta R.T., Frock R.L., Mounkes L., Barbie D.A., Stewart C.L., Harlow E., and Kennedy B.K. A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation. Proc Natl Acad Sci USA 101 (2004) 9677-9682
43. Van Berlo J.H., Voncken J.W., Kubben N., Broers J.L., Duisters R., van Leeuwen R.E., Crijns H.J., Ramaekers F.C., Hutchison C.J., and Pinto Y.M. A-type lamins are essential for TGF-β1 induced PP2A to dephosphorylate transcription factors. Hum Mol Genet 14 (2005) 2839-2849
44. Nitta R.T., Jameson S.A., Kudlow B.A., Conlan L.A., and Kennedy B.K. Stabilization of the retinoblastoma protein by A-type nuclear lamins is required for INK4A-mediated cell cycle arrest. Mol Cell Biol 26 (2006) 5360-5372
45. Favreau C., Higuet D., Courvalin J.C., and Buendia B. Expression of a mutant lamin A that causes Emery-Dreifuss muscular dystrophy inhibits in vitro differentiation of C2C12 myoblasts. Mol Cell Biol 24 (2004) 1481-1492
46. Frock R.L., Kudlow B.A., Evans A.M., Jameson S.A., Hauschka S.D., and Kennedy B.K. Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation. Genes Dev 20 (2006) 486-500. This study shows that loss of lamin A/C or emerin reduced MyoD and desmin protein levels in myoblasts and impairs myotube differentiation, and provides further evidence for the involvement of lamin complexes in striated muscle homeostasis and regeneration.
47. Bakay M., Wang Z., Melcon G., Schiltz L., Xuan J., Zhao P., Sartorelli V., Seo J., Pegoraro E., Angelini C., et al. Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb-MyoD pathways in muscle regeneration. Brain 129 (2006) 996-1013. In support of the study in reference [(46)], gene expression profiling analyses of muscle biopsies from Emery Dreifuss muscular dystrophy patients shows a deregulation of the Rb-MyoD pathway.
48. Melcon G., Kozlov S., Cutler D.A., Sullivan T., Hernandez L., Zhao P., Mitchell S., Nader G., Bakay M., Rottman J.N., et al. Loss of emerin at the nuclear envelope disrupts the Rb1/E2F and MyoD pathways during muscle regeneration. Hum Mol Genet 15 (2006) 637-651
49. Liu B., Wang J., Chan K.M., Tjia W.M., Deng W., Guan X., Huang J.D., Li K.M., Chau P.Y., Chen D.J., et al. Genomic instability in laminopathy-based premature aging. Nat Med 11 (2005) 780-785. Cells derived from HGPS patients and from a HGPS mouse model reveal defects in DNA damage response. This study suggests that like in other aging diseases, genomic instability may also play a major role in laminopathy-type premature aging.
50. Liu Y., Rusinol A., Sinensky M., Wang Y., and Zou Y. DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A. J Cell Sci 119 (2006) 4644-4649
51. Lans H., and Hoeijmakers J.H. Cell biology: ageing nucleus gets out of shape. Nature 440 (2006) 32-34
52. Manju K., Muralikrishna B., and Parnaik V.K. Expression of disease-causing lamin A mutants impairs the formation of DNA repair foci. J Cell Sci 119 (2006) 2704-2714
53. Varela I., Cadinanos J., Pendas A.M., Gutierrez-Fernandez A., Folgueras A.R., Sanchez L.M., Zhou Z., Rodriguez F.J., Stewart C.L., Vega J.A., et al. Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation. Nature 437 (2005) 564-568. This study provides evidence that nuclear abnormalities caused by accumulation of prelamin A activate a p53-dependent checkpoint response that causes senescence at the cellular level and aging at the organismal level.