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Cold Spring Harbor Perspectives in... Feb 2022Lamins interact with a host of nuclear membrane proteins, transcription factors, chromatin regulators, signaling molecules, splicing factors, and even chromatin itself... (Review)
Review
Lamins interact with a host of nuclear membrane proteins, transcription factors, chromatin regulators, signaling molecules, splicing factors, and even chromatin itself to form a nuclear subcompartment, the nuclear lamina, that is involved in a variety of cellular processes such as the governance of nuclear integrity, nuclear positioning, mitosis, DNA repair, DNA replication, splicing, signaling, mechanotransduction and -sensation, transcriptional regulation, and genome organization. Lamins are the primary scaffold for this nuclear subcompartment, but interactions with lamin-associated peptides in the inner nuclear membrane are self-reinforcing and mutually required. Lamins also interact, directly and indirectly, with peripheral heterochromatin domains called lamina-associated domains (LADs) and help to regulate dynamic 3D genome organization and expression of developmentally regulated genes.
Topics: Cell Nucleus; Chromatin; Lamins; Mechanotransduction, Cellular; Nuclear Envelope; Nuclear Lamina
PubMed: 34400553
DOI: 10.1101/cshperspect.a040113 -
Nucleus (Austin, Tex.) Jul 2017Nuclear lamins are intermediate filament proteins that represent important structural components of metazoan nuclear envelopes (NEs). By combining proteomics and...
Nuclear lamins are intermediate filament proteins that represent important structural components of metazoan nuclear envelopes (NEs). By combining proteomics and superresolution microscopy, we recently reported that both A- and B-type nuclear lamins form spatially distinct filament networks at the nuclear periphery of mouse fibroblasts. In particular, A-type lamins exhibit differential association with nuclear pore complexes (NPCs). Our studies reveal that the nuclear lamina network in mammalian somatic cells is less ordered and more complex than that of amphibian oocytes, the only other system in which the lamina has been visualized at high resolution. In addition, the NPC component Tpr likely links NPCs to the A-type lamin network, an association that appears to be regulated by C-terminal modification of various A-type lamin isoforms. Many questions remain, however, concerning the structure and assembly of lamin filaments, as well as with their mode of association with other nuclear components such as peripheral chromatin.
Topics: Animals; Fibroblasts; Lamin Type A; Lamin Type B; Metabolic Networks and Pathways; Mice; Nuclear Envelope; Protein Isoforms
PubMed: 28901826
DOI: 10.1080/19491034.2017.1296616 -
Annual Review of Pathology Jan 2022The nuclear envelope is composed of the nuclear membranes, nuclear lamina, and nuclear pore complexes. Laminopathies are diseases caused by mutations in genes encoding... (Review)
Review
The nuclear envelope is composed of the nuclear membranes, nuclear lamina, and nuclear pore complexes. Laminopathies are diseases caused by mutations in genes encoding protein components of the lamina and these other nuclear envelope substructures. Mutations in the single gene encoding lamin A and C, which are expressed in most differentiated somatic cells, cause diseases affecting striated muscle, adipose tissue, peripheral nerve, and multiple systems with features of accelerated aging. Mutations in genes encoding other nuclear envelope proteins also cause an array of diseases that selectively affect different tissues or organs. In some instances, the molecular and cellular consequences of laminopathy-causing mutations are known. However, even when these are understood, mechanisms explaining specific tissue or organ pathology remain enigmatic. Current mechanistic hypotheses focus on how alterations in the nuclear envelope may affect gene expression, including via the regulation of signaling pathways, or cellular mechanics, including responses to mechanical stress.
Topics: Humans; Lamin Type A; Laminopathies; Mutation; Signal Transduction
PubMed: 34672689
DOI: 10.1146/annurev-pathol-042220-034240 -
Cold Spring Harbor Perspectives in... Apr 2010A- and B-type lamins are the major intermediate filaments of the nucleus. Lamins engage in a plethora of stable and transient interactions, near the inner nuclear... (Review)
Review
A- and B-type lamins are the major intermediate filaments of the nucleus. Lamins engage in a plethora of stable and transient interactions, near the inner nuclear membrane and throughout the nucleus. Lamin-binding proteins serve an amazingly diverse range of functions. Numerous inner-membrane proteins help anchor lamin filaments to the nuclear envelope, serving as part of the nuclear "lamina" network that is essential for nuclear architecture and integrity. Certain lamin-binding proteins of the inner membrane bind partners in the outer membrane and mechanically link lamins to the cytoskeleton. Inside the nucleus, lamin-binding proteins appear to serve as the "adaptors" by which the lamina organizes chromatin, influences gene expression and epigenetic regulation, and modulates signaling pathways. Transient interactions of lamins with key components of the transcription and replication machinery may provide an additional level of regulation or support to these essential events.
Topics: Animals; Chromatin; Cytoskeleton; DNA-Binding Proteins; Lamins; Mice; Nuclear Envelope
PubMed: 20452940
DOI: 10.1101/cshperspect.a000554 -
Cells May 2020Mechanotransduction translates forces into biological responses and regulates cell functionalities. It is implicated in several diseases, including laminopathies which... (Review)
Review
Mechanotransduction translates forces into biological responses and regulates cell functionalities. It is implicated in several diseases, including laminopathies which are pathologies associated with mutations in lamins and lamin-associated proteins. These pathologies affect muscle, adipose, bone, nerve, and skin cells and range from muscular dystrophies to accelerated aging. Although the exact mechanisms governing laminopathies and gene expression are still not clear, a strong correlation has been found between cell functionality and nuclear behavior. New theories base on the direct effect of external force on the genome, which is indeed sensitive to the force transduced by the nuclear lamina. Nuclear lamina performs two essential functions in mechanotransduction pathway modulating the nuclear stiffness and governing the chromatin remodeling. Indeed, A-type lamin mutation and deregulation has been found to affect the nuclear response, altering several downstream cellular processes such as mitosis, chromatin organization, DNA replication-transcription, and nuclear structural integrity. In this review, we summarize the recent findings on the molecular composition and architecture of the nuclear lamina, its role in healthy cells and disease regulation. We focus on A-type lamins since this protein family is the most involved in mechanotransduction and laminopathies.
Topics: Animals; Humans; Lamin Type A; Laminopathies; Mechanotransduction, Cellular; Mutation; Protein Binding
PubMed: 32456328
DOI: 10.3390/cells9051306 -
Current Biology : CB May 2016Xie and Burke discuss the roles of lamins in nuclear morphology and the pathological consequences of defects in these nuclear envelope proteins.
Xie and Burke discuss the roles of lamins in nuclear morphology and the pathological consequences of defects in these nuclear envelope proteins.
Topics: Animals; Cell Membrane; Gene Expression Regulation; Lamins
PubMed: 27166687
DOI: 10.1016/j.cub.2016.01.055 -
Cells Mar 2019Extracellular mechanical stimuli are translated into biochemical signals inside the cell via mechanotransduction. The nucleus plays a critical role in mechanoregulation,... (Review)
Review
Extracellular mechanical stimuli are translated into biochemical signals inside the cell via mechanotransduction. The nucleus plays a critical role in mechanoregulation, which encompasses mechanosensing and mechanotransduction. The nuclear lamina underlying the inner nuclear membrane not only maintains the structural integrity, but also connects the cytoskeleton to the nuclear envelope. Lamin mutations, therefore, dysregulate the nuclear response, resulting in abnormal mechanoregulations, and ultimately, disease progression. Impaired mechanoregulations even induce malfunction in nuclear positioning, cell migration, mechanosensation, as well as differentiation. To know how to overcome laminopathies, we need to understand the mechanisms of laminopathies in a mechanobiological way. Recently, emerging studies have demonstrated the varying defects from lamin mutation in cellular homeostasis within mechanical surroundings. Therefore, this review summarizes recent findings highlighting the role of lamins, the architecture of nuclear lamina, and their disease relevance in the context of nuclear mechanobiology. We will also provide an overview of the differentiation of cellular mechanics in laminopathy.
Topics: Animals; Biophysical Phenomena; Cytoskeleton; Humans; Lamins; Mechanotransduction, Cellular; Models, Biological; Nuclear Lamina
PubMed: 30862117
DOI: 10.3390/cells8030231 -
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 -
Current Opinion in Cell Biology Jun 2020The nucleus is one of the membrane-bound organelles that are a distinguishing feature between eukaryotes and prokaryotes. During meiosis, the nuclear envelope takes on... (Review)
Review
The nucleus is one of the membrane-bound organelles that are a distinguishing feature between eukaryotes and prokaryotes. During meiosis, the nuclear envelope takes on functions beyond separating the nucleoplasm from the cytoplasm. These include associations with meiotic chromosomes to mediate pairing, being a sensor for recombination progression, and supportive of enormous nuclear growth during oocyte formation. In this review, we highlight recent results that have contributed to our understanding of meiotic nuclear envelope function and dynamics.
Topics: Animals; Chromosomes; Fertilization; Lamins; Meiosis; Nuclear Envelope; Oocytes
PubMed: 32109733
DOI: 10.1016/j.ceb.2019.12.010 -
Nucleus (Austin, Tex.) Jan 2018Lamins are evolutionarily conserved nuclear intermediate filament proteins. They provide structural support for the nucleus and help regulate many other nuclear... (Review)
Review
Lamins are evolutionarily conserved nuclear intermediate filament proteins. They provide structural support for the nucleus and help regulate many other nuclear activities. Mutations in human lamin genes, and especially in the LMNA gene, cause numerous diseases, termed laminopathies, including muscle, cardiac, metabolic, neuronal and early aging diseases. Most laminopathies arise from autosomal dominant missense mutations. Many of the mutant residues are conserved in the lamin genes of the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Our current understanding of the mechanisms leading to these diseases is mostly based on patients cell lines and animal models including C. elegans and D. melanogaster. The simpler lamin system and the powerful genetic tools offered by these invertebrate organisms greatly contributed to such studies. Here we provide an overview of the studies of laminopathies in Drosophila and C. elegans models.
Topics: Animals; Caenorhabditis elegans; Disease Models, Animal; Drosophila melanogaster; Humans; Lamins; Musculoskeletal Diseases; Mutation
PubMed: 29557730
DOI: 10.1080/19491034.2018.1454166