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Trends in Cell Biology Dec 2021Nuclear pore complexes (NPCs) are huge protein assemblies within the nuclear envelope (NE) that serve as selective gates for macromolecular transport between nucleus and... (Review)
Review
Nuclear pore complexes (NPCs) are huge protein assemblies within the nuclear envelope (NE) that serve as selective gates for macromolecular transport between nucleus and cytoplasm. When higher eukaryotic cells prepare for division, they rapidly disintegrate NPCs during NE breakdown such that nuclear and cytoplasmic components mix to enable the formation of a cytoplasmic mitotic spindle. At the end of mitosis, reassembly of NPCs is coordinated with the establishment of the NE around decondensing chromatin. We review recent progress on mitotic NPC disassembly and reassembly, focusing on vertebrate cells. We highlight novel mechanistic insights into how NPCs are rapidly disintegrated into conveniently reusable building blocks, and put divergent models of (post-)mitotic NPC assembly into a spatial and temporal context.
Topics: Cell Nucleus; Humans; Mitosis; Nuclear Envelope; Nuclear Pore; Nuclear Pore Complex Proteins
PubMed: 34294532
DOI: 10.1016/j.tcb.2021.06.011 -
International Journal of Molecular... Jan 2022Developing effective treatments for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) requires understanding of the underlying pathomechanisms that... (Review)
Review
Developing effective treatments for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) requires understanding of the underlying pathomechanisms that contribute to the motor neuron loss that defines the disease. As it causes the largest fraction of familial ALS cases, considerable effort has focused on hexanucleotide repeat expansions in the gene, which encode toxic repeat RNA and dipeptide repeat (DPR) proteins. Both the repeat RNA and DPRs interact with and perturb multiple elements of the nuclear transport machinery, including shuttling nuclear transport receptors, the Ran GTPase and the nucleoporin proteins (nups) that build the nuclear pore complex (NPC). Here, we consider recent work that describes changes to the molecular composition of the NPC in model and patient neurons in the context of quality control mechanisms that function at the nuclear envelope (NE). For example, changes to NPC structure may be caused by the dysregulation of a conserved NE surveillance pathway mediated by the endosomal sorting complexes required for the transport protein, CHMP7. Thus, these studies are introducing NE and NPC quality control pathways as key elements in a pathological cascade that leads to ALS, opening entirely new experimental avenues and possibilities for targeted therapeutic intervention.
Topics: Active Transport, Cell Nucleus; Amyotrophic Lateral Sclerosis; Homeostasis; Humans; Motor Neurons; Nuclear Pore
PubMed: 35163252
DOI: 10.3390/ijms23031329 -
Journal of Cell Science Feb 2015Nuclear pore complexes (NPCs) are indispensable for cell function and are at the center of several human diseases. NPCs provide access to the nucleus and regulate the... (Review)
Review
Nuclear pore complexes (NPCs) are indispensable for cell function and are at the center of several human diseases. NPCs provide access to the nucleus and regulate the transport of proteins and RNA across the nuclear envelope. They are aqueous channels generated from a complex network of evolutionarily conserved proteins known as nucleporins. In this Cell Science at a Glance article and the accompanying poster, we discuss how transport between the nucleoplasm and the cytoplasm is regulated, what we currently know about the structure of individual nucleoporins and the assembled NPC, and how the cell regulates assembly and disassembly of such a massive structure. Our aim is to provide a general overview on what we currently know about the nuclear pore and point out directions of research this area is heading to.
Topics: Active Transport, Cell Nucleus; Cell Line, Tumor; Cytoplasm; HeLa Cells; Humans; Nuclear Pore; Nuclear Pore Complex Proteins; RNA
PubMed: 26046137
DOI: 10.1242/jcs.083246 -
Molecular Microbiology Oct 2022Adenoviruses (AdVs) are widespread in vertebrates. They infect the respiratory and gastrointestinal tracts, the eyes, heart, liver, and kidney, and are lethal to... (Review)
Review
Adenoviruses (AdVs) are widespread in vertebrates. They infect the respiratory and gastrointestinal tracts, the eyes, heart, liver, and kidney, and are lethal to immunosuppressed people. Mastadenoviruses infecting mammals comprise several hundred different types, and many specifically infect humans. Human adenoviruses are the most widely used vectors in clinical applications, including cancer treatment and COVID-19 vaccination. AdV vectors are physically and genetically stable and generally safe in humans. The particles have an icosahedral coat and a nucleoprotein core with a DNA genome. We describe the concept of AdV cell entry and highlight recent advances in cytoplasmic transport, uncoating, and nuclear import of the viral DNA. We highlight a recently discovered "linchpin" function of the virion protein V ensuring cytoplasmic particle stability, which is relaxed at the nuclear pore complex by cues from the E3 ubiquitin ligase Mind bomb 1 (MIB1) and the proteasome triggering disruption. Capsid disruption by kinesin motor proteins and microtubules exposes the linchpin and renders protein V a target for MIB1 ubiquitination, which dissociates V from viral DNA and enhances DNA nuclear import. These advances uncover mechanisms controlling capsid stability and premature uncoating and provide insight into nuclear transport of nucleic acids.
Topics: Animals; Humans; Active Transport, Cell Nucleus; Adenoviridae; DNA, Viral; Proteasome Endopeptidase Complex; Kinesins; COVID-19 Vaccines; COVID-19; Nuclear Pore; Capsid Proteins; Ubiquitin-Protein Ligases; Nucleoproteins; Mammals
PubMed: 35434852
DOI: 10.1111/mmi.14909 -
Cold Spring Harbor Perspectives in... Jan 2022The nuclear pore complex (NPC) is a highly conserved channel in the nuclear envelope that mediates mRNA export to the cytosol and bidirectional protein transport. Many... (Review)
Review
The nuclear pore complex (NPC) is a highly conserved channel in the nuclear envelope that mediates mRNA export to the cytosol and bidirectional protein transport. Many chromosomal loci physically interact with nuclear pore proteins (Nups), and interactions with Nups can promote transcriptional repression, transcriptional activation, and transcriptional poising. Interaction with the NPC also affects the spatial arrangement of genes, interchromosomal clustering, and folding of topologically associated domains. Thus, the NPC is a spatial organizer of the genome and regulator of genome function.
Topics: Active Transport, Cell Nucleus; Genome; Nuclear Pore; Nuclear Pore Complex Proteins; Protein Transport
PubMed: 34127448
DOI: 10.1101/cshperspect.a039438 -
Cells Apr 2022Nuclear pore complexes (NPCs) are the only transport channels that cross the nuclear envelope. Constructed from ~500-1000 nucleoporin proteins each, they are among the... (Review)
Review
Nuclear pore complexes (NPCs) are the only transport channels that cross the nuclear envelope. Constructed from ~500-1000 nucleoporin proteins each, they are among the largest macromolecular assemblies in eukaryotic cells. Thanks to advances in structural analysis approaches, the construction principles and architecture of the NPC have recently been revealed at submolecular resolution. Although the overall structure and inventory of nucleoporins are conserved, NPCs exhibit significant compositional and functional plasticity even within single cells and surprising variability in their assembly pathways. Once assembled, NPCs remain seemingly unexchangeable in post-mitotic cells. There are a number of as yet unresolved questions about how the versatility of NPC assembly and composition is established, how cells monitor the functional state of NPCs or how they could be renewed. Here, we review current progress in our understanding of the key aspects of NPC architecture and lifecycle.
Topics: Eukaryotic Cells; Nuclear Envelope; Nuclear Pore; Nuclear Pore Complex Proteins
PubMed: 35563762
DOI: 10.3390/cells11091456 -
Developmental Cell Dec 2017Nuclear pore complexes tightly regulate nucleo-cytoplasmic transport, controlling the nuclear concentration of several transcription factors. In a recent issue of Cell,... (Review)
Review
Nuclear pore complexes tightly regulate nucleo-cytoplasmic transport, controlling the nuclear concentration of several transcription factors. In a recent issue of Cell, Elosegui-Artola et al. (2017) show that nuclear deformation modulates the nuclear entry rates of YAP/TAZ via nuclear pore stretching, clarifying how forces affect gene transcription.
Topics: Active Transport, Cell Nucleus; Adaptor Proteins, Signal Transducing; Animals; Cell Nucleus; Humans; Nuclear Pore; Phosphoproteins; Transcription Factors
PubMed: 29207257
DOI: 10.1016/j.devcel.2017.11.015 -
Nucleus (Austin, Tex.) Dec 2024The separation of genetic material from bulk cytoplasm has enabled the evolution of increasingly complex organisms, allowing for the development of sophisticated forms... (Review)
Review
The separation of genetic material from bulk cytoplasm has enabled the evolution of increasingly complex organisms, allowing for the development of sophisticated forms of life. However, this complexity has created new categories of dysfunction, including those related to the movement of material between cellular compartments. In eukaryotic cells, nucleocytoplasmic trafficking is a fundamental biological process, and cumulative disruptions to nuclear integrity and nucleocytoplasmic transport are detrimental to cell survival. This is particularly true in post-mitotic neurons, where nuclear pore injury and errors to nucleocytoplasmic trafficking are strongly associated with neurodegenerative disease. In this review, we summarize the current understanding of nuclear pore biology in physiological and pathological contexts and discuss potential therapeutic approaches for addressing nuclear pore injury and dysfunctional nucleocytoplasmic transport.
Topics: Humans; Nuclear Pore; Cell Nucleus; Neurodegenerative Diseases; Active Transport, Cell Nucleus; Nuclear Pore Complex Proteins
PubMed: 38383349
DOI: 10.1080/19491034.2024.2314297 -
Cell Mar 2016Nuclear pore complexes (NPCs) perforate the nuclear envelope and serve as the primary transport gates for molecular exchange between nucleus and cytoplasm. Stripping the... (Review)
Review
Nuclear pore complexes (NPCs) perforate the nuclear envelope and serve as the primary transport gates for molecular exchange between nucleus and cytoplasm. Stripping the megadalton complex down to its most essential organizational elements, one can divide the NPC into scaffold components and the disordered elements attached to them that generate a selective barrier between compartments. These structural elements exhibit flexibility, which may hold a clue in understanding NPC assembly and function. Here we review the current status of NPC research with a focus on the functional implications of its structural and compositional heterogeneity.
Topics: Animals; Evolution, Molecular; Humans; Models, Molecular; Nuclear Pore; Nuclear Pore Complex Proteins
PubMed: 26967283
DOI: 10.1016/j.cell.2016.01.034 -
Biochemical Society Transactions Aug 2021The nuclear pore complex (NPC) is responsible for transport between the cytoplasm and nucleoplasm and one of the more intricate structures of eukaryotic cells. Typically... (Review)
Review
The nuclear pore complex (NPC) is responsible for transport between the cytoplasm and nucleoplasm and one of the more intricate structures of eukaryotic cells. Typically composed of over 300 polypeptides, the NPC shares evolutionary origins with endo-membrane and intraflagellar transport system complexes. The modern NPC was fully established by the time of the last eukaryotic common ancestor and, hence, prior to eukaryote diversification. Despite the complexity, the NPC structure is surprisingly flexible with considerable variation between lineages. Here, we review diversification of the NPC in major taxa in view of recent advances in genomic and structural characterisation of plant, protist and nucleomorph NPCs and discuss the implications for NPC evolution. Furthermore, we highlight these changes in the context of mRNA export and consider how this process may have influenced NPC diversity. We reveal the NPC as a platform for continual evolution and adaptation.
Topics: Animals; Biological Evolution; Biological Transport; Membrane Proteins; Mitosis; Nuclear Pore; RNA, Messenger
PubMed: 34282823
DOI: 10.1042/BST20200570