Abstract
Nuclear lamins are type V intermediate filament proteins that polymerize into complex filamentous meshworks at the nuclear periphery and in less structured forms throughout the nucleoplasm. Lamins interact with a wide range of nuclear proteins and are involved in numerous nuclear and cellular functions. Within the nucleus, they play roles in chromatin organization and gene regulation, nuclear shape, size, and mechanics, and the organization and anchorage of nuclear pore complexes. At the whole cell level, they are involved in the organization of the cytoskeleton, cell motility, and mechanotransduction. The expression of different lamin isoforms has been associated with developmental progression, differentiation, and tissue-specific functions. Mutations in lamins and their binding proteins result in over 15 distinct human diseases, referred to as laminopathies. The laminopathies include muscular (e.g., Emery–Dreifuss muscular dystrophy and dilated cardiomyopathy), neurological (e.g., microcephaly), and metabolic (e.g., familial partial lipodystrophy) disorders as well as premature aging diseases (e.g., Hutchinson–Gilford Progeria and Werner syndromes). How lamins contribute to the etiology of laminopathies is still unknown. In this review article, we summarize major recent findings on the structure, organization, and multiple functions of lamins in nuclear and more global cellular processes.
Highlights
lamins B1 (LB1) and LB2 proteins, respectively, encoded by the LMNB1 and LMNB2 genes, are ubiquitously expressed in all mammalian cell types
These findings suggest that the stoichiometric ratio of A-type to B-type lamins regulates nuclear stiffness.[77]
This study revealed that the lamin meshwork has unique mechanical properties as demonstrated by its reversible deformation at low extension forces (
Summary
The nonrandom organization of the genome within the nucleus is essential for the regulation of gene expression and repression. Studies in mammalian cells have shown that depletion of A-type lamins in differentiated cells is sufficient to disrupt LAD organization despite the presence of B-type lamins.[37,38] These findings suggest that both A-type and B-type lamins are likely involved in organizing LADs. These findings suggest that both A-type and B-type lamins are likely involved in organizing LADs It remains unclear whether lamins directly mediate LAD organization or whether their disruption displaces lamina associated proteins that in turn organize LADs. it remains unclear whether lamins directly mediate LAD organization or whether their disruption displaces lamina associated proteins that in turn organize LADs In addition to their presence at the NL, A- and B-type lamins localize to the nucleoplasm (Fig. 1).[8,9,10] Fluorescence correlation spectroscopy studies demonstrate that A- and B-type lamins form separate, but interacting, nucleoplasmic structures; with nucleoplasmic Atype lamins being more dynamic than B-type lamins.[8] The A-type lamins have been shown to bind both heterochromatic and euchromatic regions,[39] thereby restricting the mobility of chromatin within the nucleus.[40]. These studies suggest a central role for A- and B-type lamins in chromatin organization and gene expression
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