Key Points
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The nuclear lamina is an important structural determinant for the nuclear envelope as a whole, and its functions include attaching chromatin domains to the nuclear periphery and localizing some nuclear membrane proteins. The major components of the lamina are the A-type and B-type lamins, which are members of the intermediate filament protein family.
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The expression of A-type lamins is developmentally regulated, and at least 12 distinct disorders, including Emery–Dreifuss muscular dystrophy (EDMD), are now linked to lamin A (LMNA) mutations. Studies in mice have provided insights into the tissue-specific functions of lamin A and the basis of cellular toxicity when it is mutated.
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B-type lamins, as a class, are found in all cells and have been linked to several cellular processes, including transcription, replication, spindle assembly, chromatin organization and most recently to resistance to oxidative stress. This led to a previous model in which B-type lamins were thought to be essential in all cell types.
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Knockout studies have now indicated that B-type lamins are dispensable in certain cell types and that neither A-type nor B-type lamins may be required in early embryos or embryonic stem cells. Thus, A-type and B-type lamins seem to have multiple cellular roles, and different combinations of lamin functions may be used to varying extents in different tissues.
Abstract
The nuclear lamina is an important structural determinant for the nuclear envelope as a whole, attaching chromatin domains to the nuclear periphery and localizing some nuclear envelope proteins. The major components of the lamina are the A-type and B-type lamins, which are members of the intermediate filament protein family. Whereas the expression of A-type lamins is developmentally regulated, B-type lamins, as a class, are found in all cells. The association of B-type lamins with many aspects of nuclear function has led to the view that these are essential proteins, and there is growing evidence suggesting that they regulate cellular senescence. However, B-type lamins are dispensable in certain cell types in vivo, and neither A-type nor B-type lamins may be required in early embryos or embryonic stem cells. The picture that is beginning to emerge is of a complex network of interactions at the nuclear periphery that may be defined by cell- and tissue-specific functions.
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Acknowledgements
The authors were supported by the Singapore Biomedical Research Council and the Singapore Agency for Science, Technology and Research (A*STAR). They thank O. Dreesen for helpful discussions.
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Burke, B., Stewart, C. The nuclear lamins: flexibility in function. Nat Rev Mol Cell Biol 14, 13–24 (2013). https://doi.org/10.1038/nrm3488
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DOI: https://doi.org/10.1038/nrm3488
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