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Cold Spring Harbor Perspectives in... Feb 2017SUMMARYThe nucleoskeleton is an important structural feature of the metazoan nucleus and is involved in the regulation of genome expression and maintenance. The nuclear... (Review)
Review
SUMMARYThe nucleoskeleton is an important structural feature of the metazoan nucleus and is involved in the regulation of genome expression and maintenance. The nuclear lamins are intermediate filament proteins that form a peripheral nucleoskeleton in concert with other lamin-associated proteins. Several other proteins normally found in the cytoskeleton have also been identified in the nucleus, but, as will be discussed here, their roles in forming a nucleoskeleton have not been elucidated. Nevertheless, mutations in lamins and lamin-associated proteins cause a spectrum of diseases, making them interesting targets for future research.
Topics: Humans; Nuclear Matrix; Nuclear Proteins
PubMed: 28148597
DOI: 10.1101/cshperspect.a023556 -
Comprehensive Physiology Sep 2016The nucleus is separated from the cytosol by the nuclear envelope, which is a double lipid bilayer composed of the outer nuclear membrane and the inner nuclear membrane.... (Review)
Review
The nucleus is separated from the cytosol by the nuclear envelope, which is a double lipid bilayer composed of the outer nuclear membrane and the inner nuclear membrane. The intermediate filament proteins lamin A, lamin B, and lamin C form a network underlying the inner nuclear membrane. This proteinaceous network provides the nucleus with its strength, rigidity, and elasticity. Positioned within the inner nuclear membrane are more than 150 inner nuclear membrane proteins, many of which interact directly with lamins and require lamins for their inner nuclear membrane localization. Inner nuclear membrane proteins and the nuclear lamins define the nuclear lamina. These inner nuclear membrane proteins have tissue-specific expression and diverse functions including regulating cytoskeletal organization, nuclear architecture, cell cycle dynamics, and genomic organization. Loss or mutations in lamins and inner nuclear membrane proteins cause a wide spectrum of diseases. Here, I will review the functions of the well-studied nuclear lamina proteins and the diseases associated with loss or mutations in these proteins. © 2016 American Physiological Society. Compr Physiol 6:1655-1674, 2016.
Topics: Animals; Humans; Mutation; Nuclear Envelope; Nuclear Matrix; Nuclear Matrix-Associated Proteins
PubMed: 27783855
DOI: 10.1002/cphy.c150039 -
Current Genetics Dec 2019Correlation between nuclear and cell size, the nucleocytoplasmic ratio, is a cellular phenomenon that has been reported throughout eukaryotes for more than a century but... (Review)
Review
Correlation between nuclear and cell size, the nucleocytoplasmic ratio, is a cellular phenomenon that has been reported throughout eukaryotes for more than a century but the mechanisms that achieve it are not well understood. Here, we review work that has shed light on the cellular processes involved in nuclear size control. These studies have implicated nucleocytoplasmic transport, LINC complexes, RNA processing, regulation of nuclear envelope expansion and partitioning of importin α in nuclear size control, moving us closer to a mechanistic understanding of this phenomenon.
Topics: Active Transport, Cell Nucleus; Animals; Cell Nucleus; Cell Nucleus Size; Cytoplasm; Humans; Nuclear Envelope; Nuclear Matrix; RNA, Long Noncoding; RNA, Messenger; Schizosaccharomyces
PubMed: 31147736
DOI: 10.1007/s00294-019-00999-3 -
Postepy Higieny I Medycyny... Dec 2016The nuclear matrix (NM), or nuclear skeleton, is the non-chromatin, ribonucleoproteinaceous framework that is resistant to high ionic strength buffers, nonionic... (Review)
Review
The nuclear matrix (NM), or nuclear skeleton, is the non-chromatin, ribonucleoproteinaceous framework that is resistant to high ionic strength buffers, nonionic detergents, and nucleolytic enzymes. The NM fulfills a structural role in eukaryotic cells and is responsible for maintaining the shape of the nucleus and the spatial organization of chromatin. Moreover, the NM participates in several cellular processes, such as DNA replication/repair, gene expression, RNA transport, cell signaling and differentiation, cell cycle regulation, apoptosis and carcinogenesis. Short nucleotide sequences called scaffold/matrix attachment regions (S/MAR) anchor the chromatin loops to the NM proteins (NMP). The NMP composition is dynamic and depends on the cell type and differentiation stage or metabolic activity. Alterations in the NMP composition affect anchoring of the S/MARs and thus alter gene expression. This review aims to systematize information about the skeletal structure of the nucleus, with particular emphasis on the organization of the NM and its role in selected cellular processes. We also discuss several diseases that are caused by aberrant NM structure or dysfunction of individual NM elements.
Topics: Base Sequence; Cell Nucleus; Chromatin; DNA Replication; Humans; Matrix Attachment Regions; Neoplasms; Nuclear Matrix; Nuclear Proteins
PubMed: 28026824
DOI: No ID Found -
Journal of Biomechanical Engineering Aug 2022The 2021 Summer Biomechanics, Bioengineering, and Biotransport Conference (SB3C) featured a workshop titled "The Elephant in the Room: Nuclear Mechanics and... (Review)
Review
The 2021 Summer Biomechanics, Bioengineering, and Biotransport Conference (SB3C) featured a workshop titled "The Elephant in the Room: Nuclear Mechanics and Mechanobiology." The goal of this workshop was to provide a perspective from experts in the field on the current understanding of nuclear mechanics and its role in mechanobiology. This paper reviews the major themes and questions discussed during the workshop, including historical context on the initial methods of measuring the mechanical properties of the nucleus and classifying the primary structures dictating nuclear mechanics, physical plasticity of the nucleus, the emerging role of the linker of nucleoskeleton and cytoskeleton (LINC) complex in coupling the nucleus to the cytoplasm and driving the behavior of individual cells and multicellular assemblies, and the computational models currently in use to investigate the mechanisms of gene expression and cell signaling. Ongoing questions and controversies, along with promising future directions, are also discussed.
Topics: Biophysics; Cell Nucleus; Cytoskeleton; Microtubules; Nuclear Matrix
PubMed: 35147160
DOI: 10.1115/1.4053797 -
Nucleus (Austin, Tex.) Dec 2021The nucleus, central to cellular activity, relies on both direct mechanical input as well as its molecular transducers to sense external stimuli and respond by... (Review)
Review
The nucleus, central to cellular activity, relies on both direct mechanical input as well as its molecular transducers to sense external stimuli and respond by regulating intra-nuclear chromatin organization that determines cell function and fate. In mesenchymal stem cells of musculoskeletal tissues, changes in nuclear structures are emerging as a key modulator of their differentiation and proliferation programs. In this review we will first introduce the structural elements of the nucleoskeleton and discuss the current literature on how nuclear structure and signaling are altered in relation to environmental and tissue level mechanical cues. We will focus on state-of-the-art techniques to apply mechanical force and methods to measure nuclear mechanics in conjunction with DNA, RNA, and protein visualization in living cells. Ultimately, combining real-time nuclear deformations and chromatin dynamics can be a powerful tool to study mechanisms of how forces affect the dynamics of genome function.
Topics: Biophysics; Cell Nucleus; Chromatin; Nuclear Envelope; Nuclear Matrix
PubMed: 34455929
DOI: 10.1080/19491034.2021.1962610 -
Molecular and Cellular Biology Aug 2014Much of the work on nuclear lamins during the past 15 years has focused on mutations in LMNA (the gene for prelamin A and lamin C) that cause particular muscular... (Review)
Review
Much of the work on nuclear lamins during the past 15 years has focused on mutations in LMNA (the gene for prelamin A and lamin C) that cause particular muscular dystrophy, cardiomyopathy, partial lipodystrophy, and progeroid syndromes. These disorders, often called "laminopathies," mainly affect mesenchymal tissues (e.g., striated muscle, bone, and fibrous tissue). Recently, however, a series of papers have identified important roles for nuclear lamins in the central nervous system. Studies of knockout mice uncovered a key role for B-type lamins (lamins B1 and B2) in neuronal migration in the developing brain. Also, duplications of LMNB1 (the gene for lamin B1) have been shown to cause autosome-dominant leukodystrophy. Finally, recent studies have uncovered a peculiar pattern of nuclear lamin expression in the brain. Lamin C transcripts are present at high levels in the brain, but prelamin A expression levels are very low-due to regulation of prelamin A transcripts by microRNA 9. This form of prelamin A regulation likely explains why "prelamin A diseases" such as Hutchinson-Gilford progeria syndrome spare the central nervous system. In this review, we summarize recent progress in elucidating links between nuclear lamins and neurobiology.
Topics: Animals; Humans; Lamins; Neurobiology; Nuclear Lamina
PubMed: 24842906
DOI: 10.1128/MCB.00486-14 -
International Journal of Molecular... Oct 2023Heterochromatin and euchromatin form different spatial compartments in the interphase nucleus, with heterochromatin being localized mainly at the nuclear periphery. The... (Review)
Review
Heterochromatin and euchromatin form different spatial compartments in the interphase nucleus, with heterochromatin being localized mainly at the nuclear periphery. The mechanisms responsible for peripheral localization of heterochromatin are still not fully understood. The nuclear lamina and nuclear pore complexes were obvious candidates for the role of heterochromatin binders. This review is focused on recent studies showing that heterochromatin interactions with the nuclear lamina and nuclear pore complexes maintain its peripheral localization. Differences in chromatin interactions with the nuclear envelope in cell populations and in individual cells are also discussed.
Topics: Nuclear Lamina; Nuclear Pore; Heterochromatin; Chromatin; Cell Nucleus; Nuclear Envelope
PubMed: 37958755
DOI: 10.3390/ijms242115771 -
Current Opinion in Genetics &... Aug 2022There is a long experimental history supporting the principle that RNA is essential for normal nuclear and chromatin architecture. Most of the genome is transcribed into... (Review)
Review
There is a long experimental history supporting the principle that RNA is essential for normal nuclear and chromatin architecture. Most of the genome is transcribed into RNA but only 2% of the sequence codes for proteins. In the nucleus, most non-coding RNA, packaged in proteins, is bound into structures including chromatin and a non-chromatin scaffolding, the nuclear matrix, which was first observed by electron microscopy. Removing nuclear RNA or inhibiting its transcription causes the condensation of chromatin, showing the importance of RNA in spatially and functionally organizing the genome. Today, powerful techniques for the molecular characterization of RNA and for mapping its spatial organization in the nucleus have provided molecular detail to these principles.
Topics: Cell Nucleus; Chromatin; Nuclear Matrix; RNA; Ribonucleoproteins
PubMed: 35777349
DOI: 10.1016/j.gde.2022.101940 -
F1000Research 2019Nuclear positioning plays an essential role in defining cell architecture and behaviour in both development and disease, and nuclear location frequently adjusts... (Review)
Review
Nuclear positioning plays an essential role in defining cell architecture and behaviour in both development and disease, and nuclear location frequently adjusts according to internal and external cues. For instance, during periods of migration in many cell types, the nucleus may be actively repositioned behind the microtubule-organising centre. Nuclear movement, for the most part, is dependent upon coupling of the cytoskeleton to the nuclear periphery. This is accomplished largely through SUN and KASH domain proteins, which together assemble to form LINC (linker of the nucleoskeleton and cytoskeleton) complexes spanning the nuclear envelope. SUN proteins of the inner nuclear membrane provide a connection to nuclear structures while acting as a tether for outer nuclear membrane KASH proteins. The latter contain binding sites for diverse cytoskeletal components. Recent publications highlight new aspects of LINC complex regulation revealing that the interplay between SUN and KASH partners can strongly influence how the nucleus functionally engages with different branches of the cytoskeleton.
Topics: Animals; Cytoskeleton; Membrane Proteins; Nuclear Envelope; Nuclear Matrix; Nuclear Proteins
PubMed: 30774932
DOI: 10.12688/f1000research.16877.1