Review: The Dynamics of the Nuclear Lamins during the Cell Cycle— Relationship between Structure and Function

Moir, Robert D.; Spann, Timothy P.; Lopez‐Soler, Reynold I.; Yoon, Miri; Goldman, Anne E.; Khuon, Satya; Goldman, Robert D.

doi:10.1006/jsbi.2000.4251

Cited by 113 publications

(75 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These types of changes are observed in cardiomyocytes where lamin A͞C gene is abnormal (40,41). Nuclear lamins give the nucleus its shape and are involved in chromatin organization, DNA replication, gene expression, and transmission of mechanical signals from the cell surface to the nucleus (42)(43)(44)(45)(46). We found in the present study that although there was no reduction in the cellular content of lamin A͞C, there was loss of lamin A͞C from the nuclear envelope in ER␤ Ϫ/Ϫ mice.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the ERβ ^– /–mouse heart

Förster

Kietz

Hultenby

et al. 2004

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

View full text Add to dashboard Cite

Although the heart responds to estrogen, it is not clear whether estrogen acts directly on heart muscle or indirectly by means of the vascular, immune, or nervous system. No role for estrogen receptor (ER) β in the heart has been established, but ERβ –/– mice are hypertensive, and as they age, their hearts become enlarged. Histological and ultrastructural analysis of the heart revealed a disarray of myocytes, a disruption of intercalated discs, an increase in the number and size of gap junctions, and a profound alteration in nuclear structure, concomitantly with a loss of expression of lamin A/C from the nuclear envelope. In the lungs of ERβ –/– mice, lamin A/C was located in the nuclear membrane, indicating that lamin A/C is not an ERβ-regulated gene. Immunohistochemical studies with ERβ antibodies failed to detect ERβ in the myocardium. We conclude that abnormalities in heart morphology in ERβ –/– mice are likely due to stress on the nuclear envelope as a result of the chronic sustained systolic and diastolic hypertension observed in ERβ –/– mice. Because neither ERα nor ERβ could be detected in heart muscle, the effects of estrogen on the myocardium seem to be indirect.

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization of the ERβ ^– /–mouse heart

Förster

Kietz

Hultenby

et al. 2004

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

View full text Add to dashboard Cite

show abstract

“…This indicates that Ce-lamin is apparently more stable than human lamin B1 (t1 ͞2 of Ϸ2 h; see ref. 24). GFP:Ce-lamin containing T164P, G472D, or (17).…”

Section: Point Mutations In Disease-linked Residues Can Affect Lamin mentioning

confidence: 99%

Laminopathic mutations interfere with the assembly, localization, and dynamics of nuclear lamins

Wiesel

Mattout

Melcer

et al. 2008

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

138

View full text Add to dashboard Cite

Lamins are nuclear intermediate filament proteins and the major building blocks of the nuclear lamina. Besides providing nuclear shape and mechanical stability, lamins are required for chromatin organization, transcription regulation, DNA replication, nuclear assembly, nuclear positioning, and apoptosis. Mutations in human lamins cause many different heritable diseases, affecting various tissues and causing early aging. Although many of these mutations result in nuclear deformation, their effects on lamin filament assembly are unknown. Caenorhabditis elegans has a single evolutionarily conserved lamin protein, which can form stable 10-nmthick filaments in vitro. To gain insight into the molecular basis of lamin filament assembly and the effects of laminopathic mutations on this process, we investigated mutations in conserved residues of the rod and tail domains that are known to cause various laminopathies in human. We show that 8 of 14 mutant lamins present WT-like assembly into filaments or paracrystals, whereas 6 mutants show assembly defects. Correspondingly, expressing these mutants in transgenic animals shows abnormal distribution of Ce-lamin, abnormal nuclear shape or change in lamin mobility. These findings help in understanding the role of individual residues and domains in laminopathy pathology and, eventually, promote the development of therapeutic interventions. filament assembly ͉ laminopathic diseases ͉ nuclear envelope

show abstract

“…In the lmn-1 (RNAi) embryos, there were many examples of unequal segregation of chromatin to daughter nuclei, and of chromosomes that must have been lost from one of the daughter nuclei during the cell cycle. The difference in the amount of chromatin in daughter nuclei may be also the consequence of incomplete DNA replication, since lamins have been proposed to play an essential role in the elongation step of DNA replication (Moir et al, 2000). This difference can be also due to either nuclear fragmentation or fusion of chromatin during interphase.…”

Section: Lamins May Be Involved In Chromosome Segregationmentioning

confidence: 99%

Essential Roles forCaenorhabditis elegansLamin Gene in Nuclear Organization, Cell Cycle Progression, and Spatial Organization of Nuclear Pore Complexes

Ben-Shahar

Riemer

et al. 2000

MBoC

376

360

View full text Add to dashboard Cite

Caenorhabditis elegans has a single lamin gene, designated lmn-1 (previously termed CeLam-1). Antibodies raised against the lmn-1 product (Ce-lamin) detected a 64-kDa nuclear envelope protein. Ce-lamin was detected in the nuclear periphery of all cells except sperm and was found in the nuclear interior in embryonic cells and in a fraction of adult cells. Reductions in the amount of Ce-lamin protein produce embryonic lethality. Although the majority of affected embryos survive to produce several hundred nuclei, defects can be detected as early as the first nuclear divisions. Abnormalities include rapid changes in nuclear morphology during interphase, loss of chromosomes, unequal separation of chromosomes into daughter nuclei, abnormal condensation of chromatin, an increase in DNA content, and abnormal distribution of nuclear pore complexes (NPCs). Under conditions of incomplete RNA interference, a fraction of embryos escaped embryonic arrest and continue to develop through larval life. These animals exhibit additional phenotypes including sterility and defective segregation of chromosomes in germ cells. Our observations show that lmn-1 is an essential gene in C. elegans, and that the nuclear lamins are involved in chromatin organization, cell cycle progression, chromosome segregation, and correct spacing of NPCs. INTRODUCTIONThe nuclear lamina is a filamentous meshwork that is present between the inner nuclear membrane and the peripheral chromatin. The inner nuclear membrane and the nuclear lamina are involved in organizing nuclear structure and regulating nuclear events. These include the organization of the higher order structure of chromatin and regulation of nuclear assembly and disassembly. The nuclear lamina is a primary target for caspases in apoptosis (reviewed in Goldberg et al., 1999b). Lamins are the major proteins of the nuclear lamina. They are classified as type-V intermediate filaments and are composed of an ␣-helical rod domain flanked by a short amino (head) and a long carboxy (tail) domains. The rod domain of lamins is 52-nm long and contains four ␣-helices, each composed of heptad repeats. Coiled-coil interactions and head-to-tail associations between lamin monomers form 10-to 200-nm thick lamin filaments (reviewed in Stuurman et al., 1998) In vivo, lamin filaments are closely associated with the chromatin fibers (Belmont et al., 1993). In vitro, lamins can bind interphase chromatin (Hoger et al., 1991;Yuan et al., 1991;Taniura et al., 1995;Ulitzur et al., 1997;Goldberg et al., 1999a), mitotic chromosomes (Glass and Gerace, 1990;Glass et al., 1993), or specific DNA sequences (Shoeman and Traub, 1990;Luderus et al., 1992;Luderus et al., 1994;Baricheva et al., 1996;Zhao et al., 1996). The binding site of vertebrate lamins to chromatin is localized to specific sequences in the tail domain and can be displaced with the core histones H2A and H2B (Taniura et al., 1995;Goldberg et al., 1999a).The composition of the nuclear lamina varies in different cell types and is under developmental regulation ...

show abstract

Review: The Dynamics of the Nuclear Lamins during the Cell Cycle— Relationship between Structure and Function

Cited by 113 publications

References 112 publications

Characterization of the ERβ ^– /–mouse heart

Characterization of the ERβ ^– /–mouse heart

Laminopathic mutations interfere with the assembly, localization, and dynamics of nuclear lamins

Essential Roles forCaenorhabditis elegansLamin Gene in Nuclear Organization, Cell Cycle Progression, and Spatial Organization of Nuclear Pore Complexes

Contact Info

Product

Resources

About

Review: The Dynamics of the Nuclear Lamins during the Cell Cycle— Relationship between Structure and Function

Cited by 113 publications

References 112 publications

Characterization of the ERβ – /–mouse heart

Characterization of the ERβ – /–mouse heart

Laminopathic mutations interfere with the assembly, localization, and dynamics of nuclear lamins

Essential Roles forCaenorhabditis elegansLamin Gene in Nuclear Organization, Cell Cycle Progression, and Spatial Organization of Nuclear Pore Complexes

Contact Info

Product

Resources

About

Characterization of the ERβ ^– /–mouse heart

Characterization of the ERβ ^– /–mouse heart