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Nuclear lamina remodelling and its implications for human disease

Cell and Tissue Research volume 360, pages 621–631 (2015)Cite this article

Abstract

The intermediate filament A- and B-type lamins are key architectural components of the nuclear lamina, a proteinaceous meshwork that lies underneath the inner nuclear membrane. In the past decade, many different monogenic human diseases have been linked to mutations in various components of the nuclear lamina. Mutations in LMNA (encoding lamin A and C) cause a variety of human diseases, collectively called laminopathies. These include cardiomyopathies, muscular dystrophies, lipodystrophies and progeroid syndromes. In addition, elevated levels of lamin B1, attributable to genomic duplications of the LMNB1 locus, cause adult-onset autosomal dominant leukodystrophy. The molecular mechanism(s) enabling the mutations and perturbations of the nuclear lamina to give rise to such a wide variety of diseases that affect various tissues remains unclear. The composition of the nuclear lamina changes dynamically during development, between cell types and even within the same cell during differentiation and ageing. Here, we discuss the functional and cellular aspects of lamina remodelling and their implications for the tissue-specific nature of laminopathies.

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  1. Cellular Ageing, Institute of Medical Biology, 8A Biomedical Grove, #06-06 Immunos, Singapore, 138648, Republic of Singapore

    Peh Fern Ong & Oliver Dreesen

  2. Developmental and Regenerative Biology, Institute of Medical Biology, 8A Biomedical Grove, #06-06 Immunos, Singapore, 138648, Republic of Singapore

    Alexandre Chojnowski

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  2. Peh Fern Ong
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  3. Oliver Dreesen
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Correspondence to Oliver Dreesen.

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The authors acknowledge funding from the Agency of Science, Technology and Research A*STAR, Singapore.

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Chojnowski, A., Ong, P.F. & Dreesen, O. Nuclear lamina remodelling and its implications for human disease. Cell Tissue Res 360, 621–631 (2015). https://doi.org/10.1007/s00441-014-2069-4

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  • DOI: https://doi.org/10.1007/s00441-014-2069-4

Keywords

  • Lamin A/C
  • Lamin B1
  • Laminopathies
  • Lamina remodelling
  • Hutchinson-Gilford progeria syndrome
  • Autosomal dominant leukodystrophy