The nuclear envelope, lamins and nuclear assembly

Holaska, James M.; Wilson, Katherine L.; Mansharamani, Malini

doi:10.1016/s0955-0674(02)00329-0

Cited by 116 publications

(100 citation statements)

References 65 publications

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“…However, we cannot exclude that the formation of such aberrant intranuclear accumulations did not affect other lamin A/C properties, such as the interactions with lamin A/C partners. Nuclear lamina is known to participate in the organization of nuclear pores within the nuclear membrane [39]. Since we did not find any mislocalization of RanGap1 with any of the mutants tested, we can hypothesize that the localization of nuclear pore complex within the nuclear envelope is not affected.…”

Section: Lmna Mutations Alter Lamin a And C Interactions With Their Pmentioning

confidence: 61%

Specific contribution of lamin A and lamin C in the development of laminopathies

Sylvius

Hathaway

Boudreau

et al. 2008

Experimental Cell Research

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Mutations in the lamin A/C gene are involved in multiple human disorders for which the pathophysiological mechanisms are partially understood. Conflicting results prevail regarding the organization of lamin A and C mutants within the nuclear envelope (NE) and on the interactions of each lamin to its counterpart. We over-expressed various lamin A and C mutants both independently and together in COS7 cells. When expressed alone, lamin A with cardiac/muscular disorder mutations forms abnormal aggregates inside the NE and not inside the nucleoplasm. Conversely, the equivalent lamin C organizes as intranucleoplasmic aggregates that never connect to the NE as opposed to wild type lamin C. Interestingly, the lamin C molecules present within these aggregates exhibit an abnormal increased mobility. When co-expressed, the complex formed by lamin A/C aggregates in the NE. Lamin A and C mutants for lipodystrophy behave similarly to the wild type. These findings reveal that lamins A and C may be differentially affected depending on the mutation. This results in multiple possible physiological consequences which likely contribute in the phenotypic variability of laminopathies. The inability of lamin C mutants to join the nuclear rim in the absence of lamin A is a potential pathophysiological mechanism for laminopathies.

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Section: Lmna Mutations Alter Lamin a And C Interactions With Their Pmentioning

confidence: 61%

Specific contribution of lamin A and lamin C in the development of laminopathies

Sylvius

Hathaway

Boudreau

et al. 2008

Experimental Cell Research

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“…This process could be mediated by growth regulators known to interact with lamin-containing structures such as pRb (Markiewicz et al, 2002;Ozaki et al, 1994). Alternatively, since there is a strong link between genome organisation and structures at the nuclear envelope (Bridger and Bickmore, 1998; Holaska et al, 2002) then a compromised lamina organisation may result in aberrant gene expression leading to deregulated growth. In either case it is likely that a disorganised lamina is less able to protect the genome from physical trauma particularly encountered during the upheavals of mitosis and nuclear reassembly.…”

Section: Discussionmentioning

confidence: 99%

Aging of Hutchinson–Gilford progeria syndrome fibroblasts is characterised by hyperproliferation and increased apoptosis

Bridger

Kill

2004

Experimental Gerontology

157

137

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Hutchinson -Gilford progeria syndrome is a rare genetic disorder that mimics certain aspects of aging prematurely. Recent work has revealed that mutations in the lamin A gene are a cause of the disease. We show here that cellular aging of Hutchinson -Gilford progeria syndrome fibroblasts is characterised by a period of hyperproliferation and terminates with a large increase in the rate of apoptosis. The occurrence of cells with abnormal nuclear morphology reported by others is shown to be a result of cell division since the fraction of these abnormalities increases with cellular age. Similarly, the proportion of cells with an abnormal or absent A-type lamina increases with age. These data provide clues as to the cellular basis for premature aging in HGPS and support the view that cellular senescence and tissue homeostasis are important factors in the normal aging process. q 2004 Elsevier Inc. All rights reserved.

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“…Nuclear lamins play important roles in nuclear assembly, organization, and shape (49,50). Therefore, it is not surprising that cells from patients with laminopathies contain misshapen nuclei frequently accompanied by changes in the organization of nuclear membranes, pore complexes, and chromatin (29).…”

Section: Discussionmentioning

confidence: 99%

Functions and dysfunctions of the nuclear lamin Ig-fold domain in nuclear assembly, growth, and Emery–Dreifuss muscular dystrophy

Shumaker

Lopez‐Soler²,

Adam

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The non-␣-helical C terminus of Xenopus lamin B3 (LB3T) inhibits the polymerization of lamin B3 in vitro and prevents the assembly of nuclei in Xenopus egg interphase extracts. To more precisely define the functions of LB3T in nuclear assembly, we have expressed subdomains of LB3T and determined their effects on nuclear assembly in Xenopus extracts. The results demonstrate that the Ig-fold motif (LB3T-Ig) is sufficient to inhibit lamin polymerization in vitro. Addition of the LB3T-Ig to egg extracts before the introduction of chromatin prevents chromatin decondensation and the assembly of the lamina, membranes, and pore complexes comprising the nuclear envelope. When added to assembled nuclei, LB3T-Ig prevents the further incorporation of lamin B3 into the endogenous lamina and blocks nuclear growth. The introduction of a point mutation in LB3T-Ig (R454W; LB3T-IgRW), known to cause Emery-Dreifuss muscular dystrophy when present in lamin A, does not inhibit lamin polymerization, chromatin decondensation, or nuclear assembly and growth. These results shed light on the specific alterations in lamin functions attributable to a known muscular dystrophy mutation and provide an experimental framework for revealing the effects of other mutations causing a wide range of laminopathies. ''tail'' domains (3, 4). The crystal structures of three small regions within these domains are known. These structures include coils 1A and 2B of the central rod (5) and the Ig-like fold (Ig-fold) present in the tail (6, 7). The ␣-helical rod domain is required for the formation of coiled-coil lamin dimers, which are the building blocks of higher order lamin structures. The function(s) of the Ig-fold in the nuclear lamins is unknown. In other systems, however, this motif is involved in protein-protein, protein-DNA, and protein-phospholipid interactions (6).Within nuclei, lamins are found throughout the nucleoplasm and are concentrated in the lamina, which forms an interface between the inner nuclear membrane and chromatin (8,9). During the cell cycle, the organization of lamins in interphase nuclei is not static. For example, during S-phase, lamins associate with replication factors such as proliferating cell nuclear antigen and replication factor C (10-12), whereas in mitosis, lamins are phosphorylated by the mitotic kinase cdk1 (13), causing their disassembly during nuclear envelope breakdown (14 -16). Lamins are subsequently dephosphorylated as they repolymerize around chromatin during nuclear assembly in daughter cells (17,18). The process of lamin polymerization is initiated in the anaphase-telophase transition during which B-type lamins begin to assemble on chromosomes and continues into early G 1 (9).Insights into lamin functions have been obtained from studies of the cell-free assembly of nuclei in Xenopus egg interphase extracts (19). For example, addition of the non-␣-helical Cterminal domain of Xenopus lamin B3 (LB3T) inhibits lamin polymerization, chromatin decondensation, and nuclear membrane and pore assembly (20). Other lam...

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The nuclear envelope, lamins and nuclear assembly

Cited by 116 publications

References 65 publications

Specific contribution of lamin A and lamin C in the development of laminopathies

Specific contribution of lamin A and lamin C in the development of laminopathies

Aging of Hutchinson–Gilford progeria syndrome fibroblasts is characterised by hyperproliferation and increased apoptosis

Functions and dysfunctions of the nuclear lamin Ig-fold domain in nuclear assembly, growth, and Emery–Dreifuss muscular dystrophy

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