scholarly journals Quantification of the Spatial Organization of the Nuclear Lamina as a Tool for Cell Classification

2013 ◽  
Vol 2013 ◽  
pp. 1-6
Author(s):  
Christiaan H. Righolt ◽  
Diana A. Zatreanu ◽  
Vered Raz
Keyword(s):  
Nuclear Envelope ◽  
Spatial Organization ◽  
Structural Changes ◽  
Structural Integrity ◽  
Quantitative Description ◽  
Three Dimensional ◽  
Nuclear Lamina ◽  
Cellular Functions ◽  
Cell Classification ◽  
Nuclear Stability

The nuclear lamina is the structural scaffold of the nuclear envelope that plays multiple regulatory roles in chromatin organization and gene expression as well as a structural role in nuclear stability. The lamina proteins, also referred to as lamins, determine nuclear lamina organization and define the nuclear shape and the structural integrity of the cell nucleus. In addition, lamins are connected with both nuclear and cytoplasmic structures forming a dynamic cellular structure whose shape changes upon external and internal signals. When bound to the nuclear lamina, the lamins are mobile, have an impact on the nuclear envelop structure, and may induce changes in their regulatory functions. Changes in the nuclear lamina shape cause changes in cellular functions. A quantitative description of these structural changes could provide an unbiased description of changes in cellular function. In this review, we describe how changes in the nuclear lamina can be measured from three-dimensional images of lamins at the nuclear envelope, and we discuss how structural changes of the nuclear lamina can be used for cell classification.

scholarly journals Signal Transduction across the Nuclear Envelope: Role of the LINC Complex in Bidirectional Signaling

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 124 ◽  
Author(s):  
Miki Hieda
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Nuclear Envelope ◽  
Cell Cycle Progression ◽  
Structural Integrity ◽  
Short Review ◽  
Linc Complex ◽  
Cellular Functions ◽  
Bidirectional Signaling ◽  
Extracellular Signal

The primary functions of the nuclear envelope are to isolate the nucleoplasm and its contents from the cytoplasm as well as maintain the spatial and structural integrity of the nucleus. The nuclear envelope also plays a role in the transfer of various molecules and signals to and from the nucleus. To reach the nucleus, an extracellular signal must be transmitted across three biological membranes: the plasma membrane, as well as the inner and outer nuclear membranes. While signal transduction across the plasma membrane is well characterized, signal transduction across the nuclear envelope, which is essential for cellular functions such as transcriptional regulation and cell cycle progression, remains poorly understood. As a physical entity, the nuclear envelope, which contains more than 100 proteins, functions as a binding scaffold for both the cytoskeleton and the nucleoskeleton, and acts in mechanotransduction by relaying extracellular signals to the nucleus. Recent results show that the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, which is a conserved molecular bridge that spans the nuclear envelope and connects the nucleoskeleton and cytoskeleton, is also capable of transmitting information bidirectionally between the nucleus and the cytoplasm. This short review discusses bidirectional signal transduction across the nuclear envelope, with a particular focus on mechanotransduction.

scholarly journals A lamin-independent pathway for nuclear envelope assembly.

1990 ◽  
Vol 111 (6) ◽  
pp. 2247-2259 ◽  
Author(s):  
J W Newport ◽  
K L Wilson ◽  
W G Dunphy
Keyword(s):  
Nuclear Envelope ◽  
Dna Synthesis ◽  
Structural Integrity ◽  
Nuclear Lamina ◽  
Limited Extent ◽  
Nuclear Pores ◽  
Nuclear Assembly ◽  
Nuclear Envelope Assembly ◽  
A Cell ◽  
Nuclear Envelope Formation

The nuclear envelope is composed of membranes, nuclear pores, and a nuclear lamina. Using a cell-free nuclear assembly extract derived from Xenopus eggs, we have investigated how these three components interact during nuclear assembly. We find that the Xenopus embryonic lamin protein LIII cannot bind directly to chromatin or membranes when each is present alone, but is readily incorporated into nuclei when both of the components are present together in an assembly extract. We find that depleting lamin LIII from an extract does not prevent formation of an envelope consisting of membranes and nuclear pores. However, these lamin-depleted envelopes are extremely fragile and fail to grow beyond a limited extent. This suggests that lamin assembly is not required during the initial steps of nuclear envelope formation, but is required for later growth and for maintaining the structural integrity of the envelope. We also present results showing that lamins may only be incorporated into nuclei after DNA has been encapsulated within an envelope and nuclear transport has been activated. With respect to nuclear function, our results show that the presence of a nuclear lamina is required for DNA synthesis to occur within assembled nuclei.

scholarly journals Expression of lamina proteins Lamin Dm0 and Kugelkern suppresses stem cell proliferation

2017 ◽  
Author(s):  
Roman Petrovsky ◽  
Jörg Großhans
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Target Genes ◽  
Cell Function ◽  
Nuclear Lamina ◽  
Loss Of Function ◽  
Cellular Functions ◽  
Stem Cell Proliferation ◽  
Wide Range ◽  
Nuclear Stability

AbstractThe nuclear lamina is involved in numerous cellular functions, such as gene expression, nuclear organization, nuclear stability, and cell proliferation. The mechanism underlying the involvement of lamina is often not clear, especially in physiological contexts. Here we investigate how the farnesylated lamina proteins Lamin Dm0 and Kugelkern are linked to proliferation control of intestinal stem cells (ISCs) in adult Drosophila flies by loss-of-function and gain-of-function experiments. We found that ISCs mutant for Lamin Dm0 or Kugelkern proliferate, whereas overexpression of Lamin Dm0 or Kugelkern strongly suppressed proliferation. The anti-proliferative activity is, at least in part, due to suppression of Jak/Stat but not Delta/Notch signalling. Lamin Dm0 expression suppresses Jak/Stat signalling by normalization of about 50% of the Stat target genes in ISCs.Author summaryThe nuclear lamina is a protein meshwork that lies beneath the inner side of the nuclear membrane and interacts with nuclear pores, chromatin and the cytoskeleton. Changes in proteins of the nuclear lamina cause a wide range of diseases which are often not well understood. It is hypothesized that impairment of stem cell function, as a result of lamina changes, might play a key role in some of those diseases. Here we use the well characterized Drosophila midgut as a system to investigate the role of lamina proteins Lamin Dm0 and Kugelkern on stem cell proliferation.

scholarly journals Molecular Image Analysis: Quantitative Description and Classification of the Nuclear Lamina in Human Mesenchymal Stem Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Christiaan H. Righolt ◽  
Vered Raz ◽  
Bart J. Vermolen ◽  
Roeland W. Dirks ◽  
Hans J. Tanke ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Fate ◽  
3D Structure ◽  
Quantitative Description ◽  
Human Mesenchymal Stem Cells ◽  
Nuclear Lamina ◽  
Cellular Functions ◽  
Molecular Image ◽  
Structural Framework

The nuclear lamina is an intermediate filament network that provides a structural framework for the cell nucleus. Changes in lamina structure are found during changes in cell fate such as cell division or cell death and are associated with human diseases. An unbiased method that quantifies changes in lamina shape can provide information on cells undergoing changes in cellular functions. We have developed an image processing methodology that finds and quantifies the 3D structure of the nuclear lamina. We show that measurements on such images can be used for cell classification and provide information concerning protein spatial localization in this structure. To demonstrate the efficacy of this method, we compared the lamina of unmanipulated human mesenchymal stem cells (hMSCs) at passage 4 to cells activated for apoptosis. A statistically significant classification was found between the two populations.

scholarly journals Condensins Exert Force on Chromatin-Nuclear Envelope Tethers to Mediate Nucleoplasmic Reticulum Formation in Drosophila melanogaster

2015 ◽  
Vol 5 (3) ◽  
pp. 341-352 ◽  
Author(s):  
Julianna Bozler ◽  
Huy Q Nguyen ◽  
Gregory C Rogers ◽  
Giovanni Bosco
Keyword(s):  
Nuclear Envelope ◽  
Chromatin Condensation ◽  
Three Dimensional ◽  
Nuclear Architecture ◽  
Nuclear Lamina ◽  
Dimensional Structure ◽  
Interphase Chromosome ◽  
Chromatin Compaction ◽  
Three Dimensional Structure ◽  
Nucleoplasmic Reticulum

Abstract Although the nuclear envelope is known primarily for its role as a boundary between the nucleus and cytoplasm in eukaryotes, it plays a vital and dynamic role in many cellular processes. Studies of nuclear structure have revealed tissue-specific changes in nuclear envelope architecture, suggesting that its three-dimensional structure contributes to its functionality. Despite the importance of the nuclear envelope, the factors that regulate and maintain nuclear envelope shape remain largely unexplored. The nuclear envelope makes extensive and dynamic interactions with the underlying chromatin. Given this inexorable link between chromatin and the nuclear envelope, it is possible that local and global chromatin organization reciprocally impact nuclear envelope form and function. In this study, we use Drosophila salivary glands to show that the three-dimensional structure of the nuclear envelope can be altered with condensin II-mediated chromatin condensation. Both naturally occurring and engineered chromatin-envelope interactions are sufficient to allow chromatin compaction forces to drive distortions of the nuclear envelope. Weakening of the nuclear lamina further enhanced envelope remodeling, suggesting that envelope structure is capable of counterbalancing chromatin compaction forces. Our experiments reveal that the nucleoplasmic reticulum is born of the nuclear envelope and remains dynamic in that they can be reabsorbed into the nuclear envelope. We propose a model where inner nuclear envelope-chromatin tethers allow interphase chromosome movements to change nuclear envelope morphology. Therefore, interphase chromatin compaction may be a normal mechanism that reorganizes nuclear architecture, while under pathological conditions, such as laminopathies, compaction forces may contribute to defects in nuclear morphology.

scholarly journals The nuclear envelope and its involvement in cellular stress responses

2011 ◽  
Vol 39 (6) ◽  
pp. 1795-1798 ◽  
Author(s):  
Ashraf N. Malhas ◽  
David J. Vaux
Keyword(s):  
Transcription Factors ◽  
Nuclear Envelope ◽  
Stress Responses ◽  
Structural Integrity ◽  
Cellular Stress ◽  
Cellular Functions ◽  
Different Types ◽  
Cellular Stress Responses ◽  
Development And Differentiation ◽  
The Many

The nuclear envelope is not only important for the structural integrity of the nucleus, but also involved in a number of cellular functions. It has been shown to be important for maintaining and controlling chromatin organization, sequestering transcription factors, replication, transcription and signalling. The nuclear envelope is thus important for development and differentiation, and some of its components are essential for cell viability. Among the many functions which are emerging for the nuclear envelope is its involvement in protecting the cell against different types of cellular stress. In the present paper, we review key findings which describe the roles of nuclear envelope components in responses to common types of stress conditions.

scholarly journals Three-dimensional organization of Drosophila melanogaster interphase nuclei. II. Chromosome spatial organization and gene regulation.

1987 ◽  
Vol 104 (6) ◽  
pp. 1471-1483 ◽  
Author(s):  
M Hochstrasser ◽  
J W Sedat
Keyword(s):  
Gene Regulation ◽  
Drosophila Melanogaster ◽  
Nuclear Envelope ◽  
Spatial Organization ◽  
Polytene Chromosomes ◽  
Three Dimensional ◽  
Nucleolar Organizer ◽  
Cell Types ◽  
Functional Changes ◽  
Specific Subset

In the preceding article we compared the general organization of polytene chromosomes in four different Drosophila melanogaster cell types. Here we describe experiments aimed at testing for a potential role of three-dimensional chromosome folding and positioning in modulating gene expression and examining specific chromosome interactions with different nuclear structures. By charting the configurations of salivary gland chromosomes as the cells undergo functional changes, it is shown that loci are not repositioned within the nucleus when the pattern of transcription changes. Heterologous loci show no evidence of specific physical interactions with one another in any of the cell types. However, a specific subset of chromosomal loci is attached to the nuclear envelope, and this subset is extremely similar in at least two tissues. In contrast, no specific interactions between any locus and the nucleolus are found, but the base of the X chromosome, containing the nucleolar organizer, is closely linked to this organelle. These results are used to evaluate models of gene regulation that involve the specific intranuclear positioning of gene sequences. Finally, data are presented on an unusual class of nuclear envelope structures, filled with large, electron-dense particles, that are usually associated with chromosomes.

Nesprin-3: a versatile connector between the nucleus and the cytoskeleton

2011 ◽  
Vol 39 (6) ◽  
pp. 1719-1724 ◽  
Author(s):  
Mirjam Ketema ◽  
Arnoud Sonnenberg
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Actin Filaments ◽  
Structural Integrity ◽  
Nuclear Lamina ◽  
Cross Linking ◽  
Indirect Interaction ◽  
Direct Link ◽  
Nuclear Interior

The cytoskeleton is connected to the nuclear interior by LINC (linker of nucleoskeleton and cytoskeleton) complexes located in the nuclear envelope. These complexes consist of SUN proteins and nesprins present in the inner and outer nuclear membrane respectively. Whereas SUN proteins can bind the nuclear lamina, members of the nesprin protein family connect the nucleus to different components of the cytoskeleton. Nesprin-1 and -2 can establish a direct link with actin filaments, whereas nesprin-4 associates indirectly with microtubules through its interaction with kinesin-1. Nesprin-3 is the only family member known that can link the nuclear envelope to intermediate filaments. This indirect interaction is mediated by the binding of nesprin-3 to the cytoskeletal linker protein plectin. Furthermore, nesprin-3 can connect the nucleus to microtubules by its interactions with BPAG1 (bullous pemphigoid antigen 1) and MACF (microtubule–actin cross-linking factor). In contrast with the active roles that nesprin-1, -2 and -4 have in actin- and microtubule-dependent nuclear positioning, the role of nesprin-3 is likely to be more passive. We suggest that it helps to stabilize the anchorage of the nucleus within the cytoplasm and maintain the structural integrity and shape of the nucleus.

HRSEM of the nuclear envelope (NE): Nuclear pore substructure; baskets and fibrous components

1992 ◽  
Vol 50 (1) ◽  
pp. 492-493 ◽  
Author(s):  
Martin W. Goldberg ◽  
Terence D. Allen
Keyword(s):  
Nuclear Envelope ◽  
Low Voltage ◽  
Ion Beam ◽  
Membrane Surface ◽  
Three Dimensional ◽  
Nuclear Lamina ◽  
Ring Structure ◽  
Objective Lens ◽  
Nuclear Pore ◽  
Three Dimensional Model

The nuclear envelope (NE) of eukaryotic cells has been studied for many years by a variety of em techniques yielding a three dimensional model of the nuclear pore complex (NPC) consisting of two rings (∼120nm diameter), one at the outer NE and one at the inner NE. Between the rings are eight spoke structures and a central plug. The cytoplasmic ring may be decorated with up to eight particles. The NPCs are embedded in a proteinaceous network: the nuclear lamina. Recently, low voltage HRSEM was used to show the existence of a basket-like structure attached to the nucleoplasmic ring. SEM is an ideal technique for the study of membrane surfaces. High resolution can be achieved in SEMs by the use of a field emission source which produces a high brightness probe of less than lnm diameter and a specimen stage within the objective lens, reducing chromatic abberations and production of SEIII electrons. Resolution of biological specimens can be further enhanced by coating with thin, continuous films of refractory metals such as chromium or tantalum which allows the use of higher accelerating voltages and magnifications. The NEs of Xenopus oocyte germinal vesicles have been prepared as previously described for HRSEM without detergent except they have been coated nominally with 3nm of tantalum by magnetron sputtering instead of ion beam sputtered platinum. NEs have then been examined at 30kV. The ring, plug/spoke complex and particles can all be seen at the cytoplasmic surface as well as details of the outer membrane structure and particles associated with it (Fig. 1). On the nucleoplasmic surface (Fig. 2) the inner ring is observed. It has a subunit appearance with eight filaments extending from between the subunits to a third ring structure: these make up the basket-like structure. When ‘baskets’ are close together they are joined by fibres at the ‘basket ring’ (Fig. 2). When several baskets are in close proximity these fibres form a network like a canopy over the baskets (Fig. 3). Other fibres are present on the inner membrane surface which may be membrane associated fibres or canopy fibres that have collapsed. It is uncertain which, if any, of these fibres are lamins as a further level of fibres is observed at the level of the nucleoplasmic ring when the membrane is removed with detergent (Fig. 4). These fibres are consistent with previously described lamina.

Selective digestion of nuclear envelopes from Xenopus oocyte germinal vesicles: possible structural role for the nuclear lamina

1990 ◽  
Vol 97 (3) ◽  
pp. 571-580
Author(s):  
S. Whytock ◽  
R.D. Moir ◽  
M. Stewart
Keyword(s):  
Nuclear Envelope ◽  
Xenopus Oocyte ◽  
Structural Integrity ◽  
Marked Change ◽  
Nuclear Lamina ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Structural Role ◽  
Germinal Vesicles ◽  
Pore Complexes

We have used enzymic digestion as a structural probe to investigate components of the nuclear envelope of germinal vesicles from Xenopus oocytes. Previous studies have shown that these envelopes are composed of a double membrane in which nuclear pore complexes are embedded. The nuclear pore complexes are linked to a fibrous lamina that underlies the nucleoplasmic face of the envelope. The pores are also linked by pore-connecting fibrils that attach near their cytoplasmic face. Xenopus oocyte nuclear envelopes were remarkably resistant to extraction with salt solutions and, even after treatment with 1 M NaCl or 3 M MgCl2, pores, lamina and pore-connecting fibrils remained intact. However, mild proteolysis with trypsin selectively removed the lamina fibres from Triton-extracted nuclear envelopes to leave only the pore complexes and connecting fibrils. This observation confirmed that the pore-connecting fibrils were different from the lamina fibres and were probably constructed from different proteins. Trypsin digestion followed by Triton treatment resulted in the complete disintegration of the nuclear envelope, providing direct evidence for a structural role for the lamina in maintaining envelope integrity. Digestion with ribonuclease did not produce any marked change in the structure of Triton-extracted nuclear envelopes, indicating that probably neither the pore-connecting fibrils nor the cytoplasmic granules on the pore complexes contained a substantial proportion of RNA that was vital for their structural integrity.

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