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The nuclear lamins are major determinants of nuclear architecture
Author(s) -
Goldman Robert,
Adam Stephen A.,
Goldman Anne E.,
Shimi Takeshi,
Kittisopikul Mark,
Jaqaman Khuloud,
Turgay Yagmur,
Medalia Ohad
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.255.1
Subject(s) - lamin , nuclear lamina , progeria , chromatin , biology , inner membrane , microbiology and biotechnology , premature aging , intermediate filament , genetics , nuclear protein , transcription factor , gene , cytoskeleton , nucleus , cell , mitochondrion
The major structural components of the nuclear lamina are the Type V intermediate filament proteins, the nuclear lamins. There are four nuclear lamin isoforms (Lamins A, C, B1 and B2), which interact along with their binding partners to form a molecular interface between the inner nuclear envelope membrane and chromatin, the nuclear lamina in mammalian cell nuclei. Evidence has accumulated that the lamins play important roles in DNA replication, transcription, chromatin organization, DNA damage repair, the regulation of nuclear size and shape, and the disassembly and reassembly of the nucleus during mitosis. In addition, hundreds of mutations have been discovered in the gene encoding lamins A and C that cause a wide range of human diseases known as the “laminopathies”. Our studies of the nuclear phenotypes resulting from these mutations have provided important insights into the structure and function of both the A‐ and B‐type lamins in normal cells; especially those mutations which cause typical and atypical forms of premature aging (progeria). To date our observations of progeria nuclei demonstrate that the lamins play regulatory roles in the positioning and epigenetic modifications of chromatin and in premature replicative senescence. These studies have also revealed that the A‐ and B‐type lamins form different networks within the lamina. Expanding on this finding we have carried out 3D‐Structured Illumination Microscopy (3D‐SIM) analyses to show that the 4 lamin isoforms assemble into different filamentous meshworks within the lamina of normal human diploid and mouse embryonic fibroblasts. These findings are now being correlated with higher resolution images obtained by cryo‐EM tomographic analyses. 3D‐SIM is also revealing a close association between lamin filaments in the NL and peripheral domains of heterochromatin. These associations appear to be altered in the nuclei of cells in which one or more lamins are depleted. Support or Funding Information This work is supported by National Institutes of Health grants GM106023 and the Progeria Research Foundation.