Laminopathic mutations interfere with the assembly, localization, and dynamics of nuclear lamins
Open accessAbstract
Lamins are nuclear intermediate filament proteins and the major building blocks of the nuclear lamina. Besides providing nuclear shape and mechanical stability, lamins are required for chromatin organization, transcription regulation, DNA replication, nuclear assembly, nuclear positioning, and apoptosis. Mutations in human lamins cause many different heritable diseases, affecting various tissues and causing early aging. Although many of these mutations result in nuclear deformation, their effects on lamin filament assembly are unknown. Caenorhabditis elegans has a single evolutionarily conserved lamin protein, which can form stable 10-nm-thick filaments in vitro . To gain insight into the molecular basis of lamin filament assembly and the effects of laminopathic mutations on this process, we investigated mutations in conserved residues of the rod and tail domains that are known to cause various laminopathies in human. We show that 8 of 14 mutant lamins present WT-like assembly into filaments or paracrystals, whereas 6 mutants show assembly defects. Correspondingly, expressing these mutants in transgenic animals shows abnormal distribution of Ce-lamin, abnormal nuclear shape or change in lamin mobility. These findings help in understanding the role of individual residues and domains in laminopathy pathology and, eventually, promote the development of therapeutic interventions.
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Progerin is a truncated lamin A with a hydrophobic farnesylated C-terminal.
“The aberrantly processed protein produced is called progerin, a truncated form of lamin A with a hydrophobic farnesylated C-terminal 105–112.”
From Xeroderma Pigmentosa Group A (XPA), Nucleotide Excision Repair and Regulation by ATR in Response to Ultraviolet Irradiation (2017) · cites this paper as [112]
HGPS patients suffer laminopathy due to a sporadic deficiency in proteolytic processing of prelamin A into mature lamin A.
“Hutchison-Gilford progeria syndrome (HGPS) patients suffer from a variety of laminopathy ailments due to a sporadic deficiency in the proteolytic processing of the precursor form of lamin A into the mature protein.”
From Xeroderma Pigmentosa Group A (XPA), Nucleotide Excision Repair and Regulation by ATR in Response to Ultraviolet Irradiation (2017) · cites this paper as [112]
Cites
The nuclear lamina is a meshwork of intermediate-type filaments
Aebi, U., Cohn, J., Buhle, L., & Gerace, L. (1986) · Nature · doi:10.1038/323560a0 · Cited by 982 · see citing works
Self-citationThe nuclear envelope lamina is reversibly depolymerized during mitosis
Gerace, L., & Blobel, G. (1980) · Cell · doi:10.1016/0092-8674(80)90409-2 · Cited by 962 · see citing works
The nuclear lamina comes of age
Gruenbaum, Y., Margalit, A., Goldman, R. D., Shumaker, D. K., & Wilson, K. L. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1550 · Cited by 836 · see citing works
Self-citationCreation of Low-Copy Integrated Transgenic Lines in Caenorhabditis elegans
Praitis, V., Casey, E., Collar, D. C., & Austin, J. (2001) · Genetics · doi:10.1093/genetics/157.3.1217 · Cited by 817 · see citing works
Nuclear Lamins: Their Structure, Assembly, and Interactions
Stuurman, N., Heins, S., & Aebi, U. (1998) · Journal of Structural Biology · doi:10.1006/jsbi.1998.3987 · Cited by 721 · see citing works
Self-citationHerrmann, H. O., & Aebi, U. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073823 · Cited by 693 · see citing works
Self-citation“Laminopathies”: A wide spectrum of human diseases
Worman, H. J., & Bonne, G. (2007) · Experimental Cell Research · doi:10.1016/j.yexcr.2007.03.028 · Cited by 657 · see citing works
Nuclear Membrane Proteins with Potential Disease Links Found by Subtractive Proteomics
Schirmer, E. C., Florens, L. A., Guan, T., Yates, J. R., & Gerace, L. (2003) · Science · doi:10.1126/science.1088176 · Cited by 654 · see citing works
Nuclear lamins: building blocks of nuclear architecturePreprint
Goldman, R. D., Gruenbaum, Y., Moir, R. D., Shumaker, D. K., & Spann, T. P. (2002) · Genes & Development · doi:10.1101/gad.960502 · Cited by 587 · see citing works
Self-citationNuclear Lamins: Laminopathies and Their Role in Premature Ageing
Broers, J. L. V., Ramaekers, F. C. S., Bonne, G., Yaou, R. B., & Hutchison, C. J. (2006) · Physiological Reviews · doi:10.1152/physrev.00047.2005 · Cited by 572 · see citing works
Liu, J., Ben-Shahar, T. R., Riemer, D., et al. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.11.3937 · Cited by 409 · see citing works
Stringham, E. G., Dixon, D., Jones, D. S., & Candido, E. P. M. (1992) · Molecular Biology of the Cell · doi:10.1091/mbc.3.2.221 · Cited by 321 · see citing works
Age-related changes of nuclear architecture in Caenorhabditis elegans
Haithcock, E., Dayani, Y., Neufeld, E., Zahand, A. J., Feinstein, N., Mattout, A., Gruenbaum, Y., & Liu, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506955102 · Cited by 279 · see citing works
Self-citationLee, K. K., Gruenbaum, Y., Spann, P., et al. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.9.3089 · Cited by 173 · see citing works
Self-citationNuclear lamins, diseases and aging
Mattout, A., Dechat, T., Adam, S. A., Goldman, R. D., & Gruenbaum, Y. (2006) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2006.03.007 · Cited by 167 · see citing works
Self-citationHajdu-Cronin, Y. M., Chen, W. J., & Sternberg, P. W. (2004) · Genetics · doi:10.1534/genetics.104.028423 · Cited by 149 · see citing works
Heitlinger, E., Peter, M., Lustig, A., Villiger, W., Nigg, E. A., & Aebi, U. (1992) · Journal of Structural Biology · doi:10.1016/1047-8477(92)90009-y · Cited by 129 · see citing works
Self-citationBancaud, A., Huet, S., Rabut, G. E. E., & Ellenberg, J. (2010) · Cold Spring Harbor Protocols · doi:10.1101/pdb.top90 · Cited by 128 · see citing works
Moir, R. D., Spann, T. P., Lopez‐Soler, R. I., Yoon, M., Goldman, A. E., Khuon, S., & Goldman, R. D. (2000) · Journal of Structural Biology · doi:10.1006/jsbi.2000.4251 · Cited by 121 · see citing works
Nuclear Envelope, Nuclear Lamina, and Inherited Disease
Worman, H. J., & Courvalin, J. (2005) · International review of cytology · doi:10.1016/s0074-7696(05)46006-4 · Cited by 102 · see citing works
Melcer, S., Gruenbaum, Y., & Krohne, G. (2007) · Experimental Cell Research · doi:10.1016/j.yexcr.2007.03.004 · Cited by 95 · see citing works
Self-citationLamins and lamin-associated proteins in aging and disease
Vlcek, S., & Foisner, R. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.04.001 · Cited by 94 · see citing works
Fridkin, A., Mills, E., Margalit, A., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307880101 · Cited by 88 · see citing works
Mattout, A., Goldberg, M., Tzur, Y. B., Margalit, A., & Gruenbaum, Y. (2006) · Journal of Cell Science · doi:10.1242/jcs.03325 · Cited by 73 · see citing works
Self-citationKarabinoš, A., Schünemann, J., Meyer, M., et al. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)01240-8 · Cited by 72 · see citing works
Margalit, A., Neufeld, E., Feinstein, N., Wilson, K. L., Podbilewicz, B., & Gruenbaum, Y. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200704049 · Cited by 67 · see citing works
Self-citationIntermediate filaments: novel assembly models and exciting new functions for nuclear lamins
Herrmann, H. O., & Foisner, R. (2003) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3004-0 · Cited by 60 · see citing works
Self-citationSolubility properties and specific assembly pathways of the B-type lamin from Caenorhabditis elegans
Foeger, N., Wiesel, N., Lotsch, D., et al. (2006) · Journal of Structural Biology · doi:10.1016/j.jsb.2006.03.026 · Cited by 59 · see citing works
Self-citationAssembly of A- and B-type lamins studied in vivo with the baculovirus system
Klapper, M., Exner, K., Kempf, A., Gehrig, C., Stuurman, N., Fisher, P. A., & Krohne, G. (1997) · Journal of Cell Science · doi:10.1242/jcs.110.20.2519 · Cited by 59 · see citing works
Small, J. V., & Glotzer, M. (2006) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.12.010 · Cited by 39 · see citing works
Fate of the Nuclear Lamina during Caenorhabditis elegans Apoptosis
Tzur, Y. B., Hersh, B. M., Horvitz, H. R., et al. (2002) · Journal of Structural Biology · doi:10.1006/jsbi.2002.4452 · Cited by 13 · see citing works
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Pekovic, V., & Hutchison, C. J. (2008) · Journal of Anatomy · doi:10.1111/j.1469-7580.2008.00928.x · Cited by 75 · see citing works
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- Authors
- Wiesel, N., Mattout, A., Melcer, S., Melamed-Book, N., Herrmann, H., Medalia, O., Aebi, U., & Gruenbaum, Y.
- Affiliations
- *Department of Genetics, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel;
- Hebrew University of Jerusalem (IL)
- German Cancer Research Center (DE)
- Ben-Gurion University of the Negev (IL)
- University of Basel (CH)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-01-08
- Volume
- 105
- Issue
- 1
- Pages
- 180-185
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2224182
- OpenAlex
- W1972997916
- Cited by
- 101
- References
- 31
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 4 · 2014: 7 · 2013: 6 · 2012: 4
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- Israel Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- laminopathies, nuclear lamins, nuclear lamina, nuclear shape, paracrystals, Caenorhabditis elegans
- MeSH terms
- Animals, Cell Nucleus, Crystallization, DNA, Humans, Models, Genetic, Mutation, Peptides, Urea, Conserved Sequence, Caenorhabditis elegans, Point Mutation, Mutation, Missense, Nuclear Lamina, Lamins, Microscopy, Electron, Transmission, Green Fluorescent Proteins
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