2,971 results on '"NUCLEAR pore complex"'
Search Results
202. The HIV-1 Capsid: More than Just a Delivery Package
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James, Leo C., COHEN, IRUN R., Editorial Board Member, LAJTHA, ABEL, Editorial Board Member, LAMBRIS, JOHN D., Editorial Board Member, PAOLETTI, RODOLFO, Editorial Board Member, REZAEI, NIMA, Editorial Board Member, and Greber, Urs F., editor
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- 2019
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203. Dynamics of MicroRNA Biogenesis
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Fareh, Mohamed, Gerstman, Bernard S., Editor-in-Chief, Aizawa, Masuo, Series Editor, Austin, Robert H., Series Editor, Barber, James, Series Editor, Berg, Howard C., Series Editor, Callender, Robert, Series Editor, Feher, George, Series Editor, Frauenfelder, Hans, Series Editor, Giaever, Ivar, Series Editor, Joliot, Pierre, Series Editor, Keszthelyi, Lajos, Series Editor, King, Paul W., Series Editor, Lazzi, Gianluca, Series Editor, Lewis, Aaron, Series Editor, Lindsay, Stuart M., Series Editor, Liu, Xiang Yang, Series Editor, Mauzerall, David, Series Editor, Mielczarek, Eugenie V., Series Editor, Niemz, Markolf, Series Editor, Parsegian, V. Adrian, Series Editor, Powers, Linda S., Series Editor, Prohofsky, Earl W., Series Editor, Rostovtseva, Tatiana K., Series Editor, Rubin, Andrew, Series Editor, Seibert, Michael, Series Editor, Tao, Nongjian, Series Editor, Thomas, David, Series Editor, Joo, Chirlmin, editor, and Rueda, David, editor
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- 2019
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204. High-Throughput Identification of Nuclear Envelope Protein Interactions in Schizosaccharomyces pombe Using an Arrayed Membrane Yeast-Two Hybrid Library
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Joseph M. Varberg, Jennifer M. Gardner, Scott McCroskey, Snehabala Saravanan, William D. Bradford, and Sue L. Jaspersen
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nuclear envelope ,high-throughput screening ,membrane proteins ,nuclear pore complex ,spindle pole body ,Genetics ,QH426-470 - Abstract
The nuclear envelope (NE) contains a specialized set of integral membrane proteins that maintain nuclear shape and integrity and influence chromatin organization and gene expression. Advances in proteomics techniques and studies in model organisms have identified hundreds of proteins that localize to the NE. However, the function of many of these proteins at the NE remains unclear, in part due to a lack of understanding of the interactions that these proteins participate in at the NE membrane. To assist in the characterization of NE transmembrane protein interactions we developed an arrayed library of integral and peripheral membrane proteins from the fission yeast Schizosaccharomyces pombe for high-throughput screening using the split-ubiquitin based membrane yeast two -hybrid system. We used this approach to characterize protein interactions for three conserved proteins that localize to the inner nuclear membrane: Cut11/Ndc1, Lem2 and Ima1/Samp1/Net5. Additionally, we determined how the interaction network for Cut11 is altered in canonical temperature-sensitive cut11-ts mutants. This library and screening approach is readily applicable to characterizing the interactomes of integral membrane proteins localizing to various subcellular compartments.
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- 2020
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205. Misregulation of Nucleoporins 98 and 96 leads to defects in protein synthesis that promote hallmarks of tumorigenesis
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Ajai J. Pulianmackal, Kiriaki Kanakousaki, Kerry Flegel, Olga G. Grushko, Ella Gourley, Emily Rozich, and Laura A. Buttitta
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drosophila wing ,nuclear pore complex ,ribosome biogenesis ,jnk signaling ,apoptosis ,compensatory proliferation ,Medicine ,Pathology ,RB1-214 - Abstract
Nucleoporin 98KD (Nup98) is a promiscuous translocation partner in hematological malignancies. Most disease models of Nup98 translocations involve ectopic expression of the fusion protein under study, leaving the endogenous Nup98 loci unperturbed. Overlooked in these approaches is the loss of one copy of normal Nup98 in addition to the loss of Nup96 – a second Nucleoporin encoded within the same mRNA and reading frame as Nup98 – in translocations. Nup98 and Nup96 are also mutated in a number of other cancers, suggesting that their disruption is not limited to blood cancers. We found that reducing Nup98-96 function in Drosophila melanogaster (in which the Nup98-96 shared mRNA and reading frame is conserved) de-regulates the cell cycle. We found evidence of overproliferation in tissues with reduced Nup98-96, counteracted by elevated apoptosis and aberrant signaling associated with chronic wounding. Reducing Nup98-96 function led to defects in protein synthesis that triggered JNK signaling and contributed to hallmarks of tumorigenesis when apoptosis was inhibited. We suggest that partial loss of Nup98-96 function in translocations could de-regulate protein synthesis, leading to signaling that cooperates with other mutations to promote tumorigenesis.
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- 2022
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206. Cytoplasmic nucleoporin assemblage: the cellular artwork in physiology and disease.
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Lin J and Sumara I
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- Humans, Animals, Nuclear Pore metabolism, Active Transport, Cell Nucleus, Nuclear Pore Complex Proteins metabolism, Cytoplasm metabolism
- Abstract
Nucleoporins, essential proteins building the nuclear pore, are pivotal for ensuring nucleocytoplasmic transport. While traditionally confined to the nuclear envelope, emerging evidence indicates their presence in various cytoplasmic structures, suggesting potential non-transport-related roles. This review consolidates findings on cytoplasmic nucleoporin assemblies across different states, including normal physiological conditions, stress, and pathology, exploring their structural organization, formation dynamics, and functional implications. We summarize the current knowledge and the latest concepts on the regulation of nucleoporin homeostasis, aiming to enhance our understanding of their unexpected roles in physiological and pathological processes.
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- 2024
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207. Nuclear pore dysfunction and disease: a complex opportunity.
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Fare CM and Rothstein JD
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- Humans, Cell Nucleus metabolism, Active Transport, Cell Nucleus physiology, Nuclear Pore Complex Proteins metabolism, Nuclear Pore metabolism, Neurodegenerative Diseases metabolism
- Abstract
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.
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- 2024
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208. Mechanobiology of the nucleus during the G2-M transition.
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Lima JT and Ferreira JG
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- Mitosis, Cytoskeleton metabolism, Biophysics, Mechanotransduction, Cellular, Cell Nucleus metabolism
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Cellular behavior is continuously influenced by mechanical forces. These forces span the cytoskeleton and reach the nucleus, where they trigger mechanotransduction pathways that regulate downstream biochemical events. Therefore, the nucleus has emerged as a regulator of cellular response to mechanical stimuli. Cell cycle progression is regulated by cyclin-CDK complexes. Recent studies demonstrated these biochemical pathways are influenced by mechanical signals, highlighting the interdependence of cellular mechanics and cell cycle regulation. In particular, the transition from G2 to mitosis (G2-M) shows significant changes in nuclear structure and organization, ranging from nuclear pore complex (NPC) and nuclear lamina disassembly to chromosome condensation. The remodeling of these mechanically active nuclear components indicates that mitotic entry is particularly sensitive to forces. Here, we address how mechanical forces crosstalk with the nucleus to determine the timing and efficiency of the G2-M transition. Finally, we discuss how the deregulation of nuclear mechanics has consequences for mitosis.
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- 2024
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209. A lineage-specific protein network at the trypanosome nuclear envelope.
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Butterfield ER, Obado SO, Scutts SR, Zhang W, Chait BT, Rout MP, and Field MC
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- Humans, Nuclear Pore metabolism, Saccharomyces cerevisiae metabolism, Nuclear Pore Complex Proteins metabolism, Nuclear Envelope metabolism, Trypanosoma metabolism
- Abstract
The nuclear envelope (NE) separates translation and transcription and is the location of multiple functions, including chromatin organization and nucleocytoplasmic transport. The molecular basis for many of these functions have diverged between eukaryotic lineages. Trypanosoma brucei , a member of the early branching eukaryotic lineage Discoba, highlights many of these, including a distinct lamina and kinetochore composition. Here, we describe a cohort of proteins interacting with both the lamina and NPC, which we term l amina- a ssociated p roteins (LAPs). LAPs represent a diverse group of proteins, including two candidate NPC-anchoring pore membrane proteins (POMs) with architecture conserved with S. cerevisiae and H. sapiens , and additional peripheral components of the NPC. While many of the LAPs are Kinetoplastid specific, we also identified broadly conserved proteins, indicating an amalgam of divergence and conservation within the trypanosome NE proteome, highlighting the diversity of nuclear biology across the eukaryotes, increasing our understanding of eukaryotic and NPC evolution.
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- 2024
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210. Sculpting nuclear envelope identity from the endoplasmic reticulum during the cell cycle.
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Deolal P, Scholz J, Ren K, Bragulat-Teixidor H, and Otsuka S
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- Endoplasmic Reticulum metabolism, Mitosis, Active Transport, Cell Nucleus, Nuclear Envelope metabolism, Nuclear Pore metabolism
- Abstract
The nuclear envelope (NE) regulates nuclear functions, including transcription, nucleocytoplasmic transport, and protein quality control. While the outer membrane of the NE is directly continuous with the endoplasmic reticulum (ER), the NE has an overall distinct protein composition from the ER, which is crucial for its functions. During open mitosis in higher eukaryotes, the NE disassembles during mitotic entry and then reforms as a functional territory at the end of mitosis to reestablish nucleocytoplasmic compartmentalization. In this review, we examine the known mechanisms by which the functional NE reconstitutes from the mitotic ER in the continuous ER-NE endomembrane system during open mitosis. Furthermore, based on recent findings indicating that the NE possesses unique lipid metabolism and quality control mechanisms distinct from those of the ER, we explore the maintenance of NE identity and homeostasis during interphase. We also highlight the potential significance of membrane junctions between the ER and NE.
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- 2024
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211. Nuclear and degradative functions of the ESCRT-III pathway: implications for neurodegenerative disease.
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Keeley O and Coyne AN
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- Humans, Animals, Cell Nucleus metabolism, Frontotemporal Dementia metabolism, Frontotemporal Dementia pathology, Frontotemporal Dementia genetics, Endosomes metabolism, Endosomal Sorting Complexes Required for Transport metabolism, Neurodegenerative Diseases metabolism, Neurodegenerative Diseases pathology, Neurodegenerative Diseases genetics
- Abstract
The ESCRT machinery plays a pivotal role in membrane-remodeling events across multiple cellular processes including nuclear envelope repair and reformation, nuclear pore complex surveillance, endolysosomal trafficking, and neuronal pruning. Alterations in ESCRT-III functionality have been associated with neurodegenerative diseases including Frontotemporal Dementia (FTD), Amyotrophic Lateral Sclerosis (ALS), and Alzheimer's Disease (AD). In addition, mutations in specific ESCRT-III proteins have been identified in FTD/ALS. Thus, understanding how disruptions in the fundamental functions of this pathway and its individual protein components in the human central nervous system (CNS) may offer valuable insights into mechanisms underlying neurodegenerative disease pathogenesis and identification of potential therapeutic targets. In this review, we discuss ESCRT components, dynamics, and functions, with a focus on the ESCRT-III pathway. In addition, we explore the implications of altered ESCRT-III function for neurodegeneration with a primary emphasis on nuclear surveillance and endolysosomal trafficking within the CNS.
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- 2024
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212. Not just binary: embracing the complexity of nuclear division dynamics.
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Walsh ME, King GA, and Ünal E
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- Humans, Animals, Cell Nucleus metabolism, Nuclear Envelope metabolism, Chromosomes metabolism, Active Transport, Cell Nucleus, Cell Nucleus Division
- Abstract
Cell division presents a challenge for eukaryotic cells: how can chromosomes effectively segregate within the confines of a membranous nuclear compartment? Different organisms have evolved diverse solutions by modulating the degree of nuclear compartmentalization, ranging from complete nuclear envelope breakdown to complete maintenance of nuclear compartmentalization via nuclear envelope expansion. Many intermediate forms exist between these extremes, suggesting that nuclear dynamics during cell division are surprisingly plastic. In this review, we highlight the evolutionary diversity of nuclear divisions, focusing on two defining characteristics: (1) chromosome compartmentalization and (2) nucleocytoplasmic transport. Further, we highlight recent evidence that nuclear behavior during division can vary within different cellular contexts in the same organism. The variation observed within and between organisms underscores the dynamic evolution of nuclear divisions tailored to specific contexts and cellular requirements. In-depth investigation of diverse nuclear divisions will enhance our understanding of the nucleus, both in physiological and pathological states.
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- 2024
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213. Crowding-induced phase separation of nuclear transport receptors in FG nucleoporin assemblies
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Luke K Davis, Ian J Ford, and Bart W Hoogenboom
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nuclear pore complex ,phase separation ,nucleocytoplasmic transport ,biophysics ,computer modelling ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
The rapid (
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- 2022
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214. On the Nuclear Pore Complex and Its Roles in Nucleo-Cytoskeletal Coupling and Mechanobiology
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Soheilypour, M, Peyro, M, Jahed, Z, and Mofrad, MRK
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Nuclear pore complex ,SUN ,KASH ,LINC ,Mechanotransduction ,Nuclear envelope ,1.1 Normal biological development and functioning ,Underpinning research ,Biomedical Engineering - Abstract
The nuclear pore complex (NPC) is primarily recognized for its function as the gateway for nucleocytoplasmic traffic, regulating biochemical exchange between the cytoplasm and the nucleoplasm. On the other hand, the LINC complex, comprised of SUN-domain and KASH-domain proteins, is typically credited as the main physical bridge across the nuclear envelope. However, recent evidence suggests that the NPC is also directly engaged with the cytoskeletal elements and the nucleoskeleton, and as such provides a direct physical association between the nucleus and the cytoskeleton. Moreover, by controlling the transport of inner nuclear membrane proteins, including components of the LINC complex, the NPC plays additional roles in physically connecting the cytoskeleton and the nucleus. This review examines the NPC’s direct and indirect contributions to nucleo-cytoskeletal coupling and mechanobiology.
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- 2016
215. Evolution of a transcriptional regulator from a transmembrane nucleoporin
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Franks, Tobias M, Benner, Chris, Narvaiza, Iñigo, Marchetto, Maria CN, Young, Janet M, Malik, Harmit S, Gage, Fred H, and Hetzer, Martin W
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Human Genome ,Genetics ,Biotechnology ,Underpinning research ,1.1 Normal biological development and functioning ,Generic health relevance ,5' Untranslated Regions ,Cell Membrane ,Cell Nucleus ,Evolution ,Molecular ,Exons ,Gene Expression Regulation ,HeLa Cells ,Humans ,Membrane Glycoproteins ,Mutant Proteins ,Nuclear Localization Signals ,Nuclear Pore Complex Proteins ,Nuclear Proteins ,Promoter Regions ,Genetic ,Protein Domains ,Protein Isoforms ,Solubility ,Transcription Factors ,Transcription Initiation Site ,Transcription ,Genetic ,evolution ,hominoid ,Pom121 ,Nup98 ,transcription ,nuclear pore complex ,Hela Cells ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Developmental Biology - Abstract
Nuclear pore complexes (NPCs) emerged as nuclear transport channels in eukaryotic cells ∼1.5 billion years ago. While the primary role of NPCs is to regulate nucleo-cytoplasmic transport, recent research suggests that certain NPC proteins have additionally acquired the role of affecting gene expression at the nuclear periphery and in the nucleoplasm in metazoans. Here we identify a widely expressed variant of the transmembrane nucleoporin (Nup) Pom121 (named sPom121, for "soluble Pom121") that arose by genomic rearrangement before the divergence of hominoids. sPom121 lacks the nuclear membrane-anchoring domain and thus does not localize to the NPC. Instead, sPom121 colocalizes and interacts with nucleoplasmic Nup98, a previously identified transcriptional regulator, at gene promoters to control transcription of its target genes in human cells. Interestingly, sPom121 transcripts appear independently in several mammalian species, suggesting convergent innovation of Nup-mediated transcription regulation during mammalian evolution. Our findings implicate alternate transcription initiation as a mechanism to increase the functional diversity of NPC components.
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- 2016
216. Characterizing nuclear remodeling during budding yeast meiosis
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King, Grant Austin
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Cellular biology ,Genetics ,Aging ,Aging ,Budding yeast ,Cell division ,Meiosis ,Nuclear envelope ,Nuclear pore complex - Abstract
The nucleus, the defining organelle of the eukaryotic cell, must be remodeled during every cell division in order to accommodate the division of genetic material. While this remodeling has been extensively studied during mitosis, it remains poorly understood how the nucleus is remodeled during meiosis. In this study, we provide a comprehensive analysis of nuclear behavior during meiosis in the model organism budding yeast. First, we find that the nuclear envelope undergoes a five-way division, forming a nuclear-envelope bound compartment that is excluded from gametes. This compartment, termed the Gametogenesis Uninherited Nuclear Compartment or GUNC, contains nuclear pore complexes (NPCs) in all cells and age-induced damage in old cells. The material sequestered to the GUNC is subsequently eliminated by release of vacuolar proteases, establishing this remodeling event as a novel nuclear quality control mechanism that contributes to meiotic cellular rejuvenation. Second, we find that the NPC undergoes two mechanistically-distinct meiotic remodeling events: partial nuclear basket detachment during meiosis I and full nuclear basket detachment during meiosis II. Meiosis I detachment, which involves Nup60 and its binding partner Nup2, is driven by Polo kinase-dependent phosphorylation of Nup60 at its binding interface with the NPC core. Notably, this remodeling event also occurs in the distantly related Schizosaccharomyces pombe, suggesting basket detachment involves conserved nuclear basket organizational principles and fulfills an important function. Finally, we find that the nuclear permeability barrier is transiently disrupted during meiosis II, driving intermixing of the cytoplasm and nucleoplasm. Since the nuclear envelope stays intact throughout meiosis, regulation of nuclear transport machinery is likely involved in this event. Several meiotic regulators disrupt barrier loss or return, although their precise mechanistic contributions remain unclear. In all, this work establishes the nuclear periphery as a highly dynamic and regulated entity during budding yeast meiosis. Studying the budding yeast meiotic nucleus will continue to improve our understanding of nuclear organization and its contributions to cellular health for years to come.
- Published
- 2022
217. A single-molecule localization microscopy method for tissues reveals nonrandom nuclear pore distribution in Drosophila.
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Jinmei Cheng, Allgeyer, Edward S., Richens, Jennifer H., Dzafic, Edo, Palandri, Amandine, Lewków, Bohdan, Sirinakis, George, and St Johnston, Daniel
- Subjects
- *
DROSOPHILA , *MICROSCOPY , *OPTICAL aberrations , *CLUSTER theory (Nuclear physics) , *NUCLEOPORINS - Abstract
Single-molecule localization microscopy (SMLM) can provide nanoscale resolution in thin samples but has rarely been applied to tissues because of high background from out-of-focus emitters and optical aberrations. Here, we describe a line scanning microscope that provides optical sectioning for SMLM in tissues. Imaging endogenously-tagged nucleoporins and F-actin on this system using DNA- and peptide-point accumulation for imaging in nanoscale topography (PAINT) routinely gives 30 nm resolution or better at depths greater than 20 αm. This revealed that the nuclear pores are nonrandomly distributed in most Drosophila tissues, in contrast to what is seen in cultured cells. Lamin Dm0 shows a complementary localization to the nuclear pores, suggesting that it corrals the pores. Furthermore, ectopic expression of the tissue-specific Lamin C causes the nuclear pores to distribute more randomly, whereas lamin C mutants enhance nuclear pore clustering, particularly in muscle nuclei. Given that nucleoporins interact with specific chromatin domains, nuclear pore clustering could regulate local chromatin organization and contribute to the disease phenotypes caused by human lamin A/C laminopathies. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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218. Mitotic disassembly and reassembly of nuclear pore complexes.
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Kutay, Ulrike, Jühlen, Ramona, and Antonin, Wolfram
- Subjects
- *
NUCLEAR membranes , *MICROTUBULES , *SPINDLE apparatus , *ENDOPLASMIC reticulum , *CHROMATIN , *EUKARYOTIC cells , *MITOSIS , *CELL division - Abstract
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. NPC disintegration requires the combined activity of multiple mitotic kinases and exploits multisite phosphorylation, linking it to mitotic commitment. NPC disassembly generates smaller building blocks that are conveniently reusable during mitotic exit, and some of these may even remain membrane-associated throughout mitosis and serve as templates for NPC reassembly. Enclosure of all chromatin into a single nucleus that contains transport-competent NPCs requires chromosome clustering and the coordination of NPC assembly and NE reformation. Mitotic NPC reassembly starts at lateral areas of the decondensing chromatin mass, away from spindle microtubules, possibly by attraction of perforated endoplasmic reticulum (ER) membrane sheets to defined NPC assembly sites on chromatin. NPC reassembly during mitotic exit may encompass a range of modes whose prevalence is spatially and temporarily determined. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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219. Regulation of diverse nuclear shapes: pathways working independently, together.
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Deolal, Pallavi and Mishra, Krishnaveni
- Subjects
- *
NUCLEAR shapes , *CELL physiology , *MEMBRANE lipids , *NUCLEAR proteins , *NUCLEAR membranes , *UNICELLULAR organisms , *CELL compartmentation , *EUKARYOTIC cells - Abstract
Membrane-bound organelles provide physical and functional compartmentalization of biological processes in eukaryotic cells. The characteristic shape and internal organization of these organelles is determined by a combination of multiple internal and external factors. The maintenance of the shape of nucleus, which houses the genetic material within a double membrane bilayer, is crucial for a seamless spatio-temporal control over nuclear and cellular functions. Dynamic morphological changes in the shape of nucleus facilitate various biological processes. Chromatin packaging, nuclear and cytosolic protein organization, and nuclear membrane lipid homeostasis are critical determinants of overall nuclear morphology. As such, a multitude of molecular players and pathways act together to regulate the nuclear shape. Here, we review the known mechanisms governing nuclear shape in various unicellular and multicellular organisms, including the non-spherical nuclei and non-lamin-related structural determinants. The review also touches upon cellular consequences of aberrant nuclear morphologies. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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220. Chromatin mobility and relocation in DNA repair.
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Lamm, Noa, Rogers, Samuel, and Cesare, Anthony J.
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- *
CHROMATIN , *NUCLEAR membranes , *DOUBLE-strand DNA breaks , *DNA damage , *NUCLEAR proteins , *DNA repair , *DNA helicases - Abstract
The nucleus is a dynamic environment containing chromatin, membraneless organelles, and specialized molecular structures at the nuclear membrane. Within the spectrum of DNA repair activities are observations of increased mobility of damaged chromatin and the displacement of DNA lesions to specific nuclear environments. Here, we focus on the role that nuclear-specific filamentous actin plays in mobilizing damaged chromatin in response to DNA double-strand breaks and replication stress. We also examine nuclear pore complexes and promyelocytic leukemia-nuclear bodies as specialized platforms for homology-directed repair. The literature suggests an emerging model where specific types of DNA lesions are subjected to nuclear-derived forces that mobilize damaged chromatin and promote interaction with repair hubs to facilitate specialized repair reactions. Chromatin mobility contributes to the homology directed repair (HDR) of double strand breaks (DSBs) and replication stress, with some DNA lesions specifically translocated to nuclear hubs of HDR activity. Polymerization of nucleus-specific filamentous action (F-actin) promotes DSB and stalled replication fork mobility, including the directed movement of lesions along F-actin to the nuclear periphery. Nuclear pore complexes (NPC) participate in the HDR of stalled replication forks, eroded telomeres, and persistent DSBs, potentially through the break‐induced‐replication (BIR) pathway. In the 10% of human tumors that utilize alternative lengthening of telomeres (ALT), chromosome ends are mobilized to promyelocytic leukemia protein nuclear bodies (PML-NBs), which function as hubs of telomere HDR activity. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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221. Nucleo–cytoplasmic transport defects and protein aggregates in neurodegeneration
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Giacomo Bitetto and Alessio Di Fonzo
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Aging ,Neurodegeneration ,Neurodegenerative disease ,Nucleo–cytoplasmic transport ,Nuclear pore complex ,Protein aggregate ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract In the ongoing process of uncovering molecular abnormalities in neurodegenerative diseases characterized by toxic protein aggregates, nucleo-cytoplasmic transport defects have an emerging role. Several pieces of evidence suggest a link between neuronal protein inclusions and nuclear pore complex (NPC) damage. These processes lead to oxidative stress, inefficient transcription, and aberrant DNA/RNA maintenance. The clinical and neuropathological spectrum of NPC defects is broad, ranging from physiological aging to a suite of neurodegenerative diseases. A better understanding of the shared pathways among these conditions may represent a significant step toward dissecting their underlying molecular mechanisms, opening the way to a real possibility of identifying common therapeutic targets.
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- 2020
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222. Two Nucleoporin98 homologous genes jointly participate in the regulation of starch degradation to repress senescence in Arabidopsis
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Long Xiao, Shanshan Jiang, Penghui Huang, Fulu Chen, Xu Wang, Zhiyuan Cheng, Yuchen Miao, Liangyu Liu, Iain Searle, Chunyan Liu, Xiao-Xia Wu, Yong-Fu Fu, Qingshan Chen, and Xiao-Mei Zhang
- Subjects
Nup98 ,Starch ,Sugar ,Senescence ,Nuclear pore complex ,Nucleoporin ,Botany ,QK1-989 - Abstract
Abstract Background Starch is synthesized during daylight for temporary storage in leaves and then degraded during the subsequent night to support plant growth and development. Impairment of starch degradation leads to stunted growth, even senescence and death. The nuclear pore complex is involved in many cellular processes, but its relationship with starch degradation has been unclear until now. We previously identified that two Nucleoporin98 genes (Nup98a and Nup98b) redundantly regulate flowering via the CONSTANS (CO)-independent pathway in Arabidopsis thaliana. The double mutant also shows severe senescence phenotypes. Results We find that Nucleoporin 98 participates in the regulation of sugar metabolism in leaves and is also involved in senescence regulation in Arabidopsis. We show that Nup98a and Nup98b function redundantly at different stages of starch degradation. The nup98a-1 nup98b-1 double mutant accumulates more starch, showing a severe early senescence phenotype compared to wild type plants. The expression of marker genes related to starch degradation is impaired in the nup98a-1 nup98b-1 double mutant, and marker genes of carbon starvation and senescence express their products earlier and in higher abundance than in wild type plants, suggesting that abnormalities in energy metabolism are the main cause of senescence in the double mutant. Addition of sucrose to the growth medium rescues early senescence phenotypes of the nup98a-1 nup98b-1 mutant. Conclusions Our results provide evidence for a novel role of the nuclear pore complex in energy metabolism related to growth and development, in which Nup98 functions in starch degradation to control growth regulation in Arabidopsis.
- Published
- 2020
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223. The ESCRT-III complex is required for nuclear pore complex sequestration and regulates gamete replicative lifespan in budding yeast meiosis
- Author
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Bailey A. Koch, Elizabeth Staley, Hui Jin, and Hong-Guo Yu
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escrt-iii ,lem-domain protein ,nuclear pore complex ,nuclear envelope ,meiosis ,replicative lifespan ,cellular aging ,Genetics ,QH426-470 ,Cytology ,QH573-671 - Abstract
Cellular aging occurs as a cell loses its ability to maintain homeostasis. Aging cells eliminate damaged cellular compartments and other senescence factors via self-renewal. The mechanism that regulates cellular rejuvenation remains to be further elucidated. Using budding yeast gametogenesis as a model, we show here that the endosomal sorting complex required for transport (ESCRT) III regulates nuclear envelope organization. During gametogenesis, the nuclear pore complex (NPC) and other senescence factors are sequestered away from the prospore nuclei. We show that the LEM-domain protein Heh1 (Src1) facilitates the nuclear recruitment of ESCRT-III, which is required for meiotic NPC sequestration and nuclear envelope remodeling. Furthermore, ESCRT-III-mediated nuclear reorganization appears to be critical for gamete rejuvenation, as hindering this process curtails either directly or indirectly the replicative lifespan in gametes. Our findings demonstrate the importance of ESCRT-III in nuclear envelope remodeling and its potential role in eliminating senescence factors during gametogenesis.
- Published
- 2020
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224. The coordination of nuclear envelope assembly and chromosome segregation in metazoans
- Author
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Shiwei Liu and David Pellman
- Subjects
nuclear envelope ,nuclear pore complex ,mitosis ,chromosome segregation ,micronucleus ,Genetics ,QH426-470 ,Cytology ,QH573-671 - Abstract
The nuclear envelope (NE) is composed of two lipid bilayer membranes that enclose the eukaryotic genome. In interphase, the NE is perforated by thousands of nuclear pore complexes (NPCs), which allow transport in and out of the nucleus. During mitosis in metazoans, the NE is broken down and then reassembled in a manner that enables proper chromosome segregation and the formation of a single nucleus in each daughter cell. Defects in coordinating NE reformation and chromosome segregation can cause aberrant nuclear architecture. This includes the formation of micronuclei, which can trigger a catastrophic mutational process commonly observed in cancers called chromothripsis. Here, we discuss the current understanding of the coordination of NE reformation with chromosome segregation during mitotic exit in metazoans. We review differing models in the field and highlight recent work suggesting that normal NE reformation and chromosome segregation are physically linked through the timing of mitotic spindle disassembly.
- Published
- 2020
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225. Deletion of low-density lipoprotein-related receptor 5 inhibits liver Cancer cell proliferation via destabilizing Nucleoporin 37
- Author
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Jinxiao Chen, Da Wo, En Ma, Hongwei Yan, Jun Peng, Weidong Zhu, Yong Fang, and Dan-ni Ren
- Subjects
LRP5 ,NUP37 ,Nuclear pore complex ,Wnt/β-catenin signaling ,Cancer cell proliferation ,Medicine ,Cytology ,QH573-671 - Abstract
Abstract Background LRP5/6 are co-receptors in Wnt/β-catenin pathway. Recently, we discovered multiple β-catenin independent functions of LRP5/6 in tumor cells and in the diseased heart. Nucleoporin 37 (NUP37) is an important component of the nuclear pore complex (NPC), whose elevated expression is associated with worsened prognosis in liver cancer. Previous studies have shown that NUP37 interacted with YAP and activated YAP/TEAD signaling in liver cancer. Our preliminary findings showed a nuclear location of LRP5. We thus tested the hypothesis that LRP5 may act as a genuine regulator of YAP/TEAD signaling via modulating NUP37 in a β-catenin-independent way. Methods We performed siRNA knockdown of LRP5, LRP6, or β-catenin in liver cancer HepG2 cells to determine the effect on tumor cell proliferation. Protein expressions and interaction between LRP5 and NUP37 were determined using immunoprecipitation and western blot analyses. Results HepG2 cell proliferation was markedly inhibited by knockdown of LRP5 but not LRP6 or β-catenin, suggesting that LRP5 has a specific, β-catenin-independent role in inhibiting HepG2 cell proliferation. Knockdown of NUP37 by siRNA inhibited the proliferation of HepG2 cells, whereas overexpression of NUP37 reversed the decrease in cell proliferation induced by LRP5 knockdown. Immunoprecipitation assays confirmed that LRP5 bound to NUP37. Furthermore, LRP5 overexpression restored NUP37 knockdown-induced downregulation of YAP/TEAD pathway. Conclusions LRP5 deletion attenuates cell proliferation via destabilization of NUP37, in a β-catenin-independent manner. LRP5 therefore acts as a genuine regulator of YAP/TEAD signaling via maintaining the integrity of the NPC, and implicates a therapeutic strategy in targeting LRP5 for inhibiting liver cancer cell proliferation.
- Published
- 2019
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226. Fragile X–Related Protein 1 Regulates Nucleoporin Localization in a Cell Cycle–Dependent Manner
- Author
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Arantxa Agote-Arán, Junyan Lin, and Izabela Sumara
- Subjects
cell cycle ,G1 phase ,nucleoporins ,nuclear pore complex ,phase separation ,FXR1 ,Biology (General) ,QH301-705.5 - Abstract
Nuclear pore complexes (NPCs) are embedded in the nuclear envelope (NE) where they ensure the transport of macromolecules between the nucleus and the cytoplasm. NPCs are built from nucleoporins (Nups) through a sequential assembly order taking place at two different stages during the cell cycle of mammalian cells: at the end of mitosis and during interphase. In addition, fragile X–related proteins (FXRPs) can interact with several cytoplasmic Nups and facilitate their localization to the NE during interphase likely through a microtubule-dependent mechanism. In the absence of FXRPs or microtubule-based transport, Nups aberrantly localize to the cytoplasm forming the so-called cytoplasmic nucleoporin granules (CNGs), compromising NPCs’ function on protein export. However, it remains unknown if Nup synthesis or degradation mechanisms are linked to the FXRP–Nup pathway and if and how the action of FXRPs on Nups is coordinated with the cell cycle progression. Here, we show that Nup localization defects observed in the absence of FXR1 are independent of active protein translation. CNGs are cleared in an autophagy- and proteasome-independent manner, and their presence is restricted to the early G1 phase of the cell cycle. Our results thus suggest that a pool of cytoplasmic Nups exists that contributes to the NPC assembly specifically during early G1 to ensure NPC homeostasis at a short transition from mitosis to the onset of interphase.
- Published
- 2021
- Full Text
- View/download PDF
227. A short perinuclear amphipathic α-helix in Apq12 promotes nuclear pore complex biogenesis
- Author
-
Wanlu Zhang, Azqa Khan, Jlenia Vitale, Annett Neuner, Kerstin Rink, Christian Lüchtenborg, Britta Brügger, Thomas H. Söllner, and Elmar Schiebel
- Subjects
APQ12 ,BRR6 ,nuclear pore complex ,nuclear envelope ,BRL1 ,nuclear pore complex biogenesis ,Biology (General) ,QH301-705.5 - Abstract
The integral membrane protein Apq12 is an important nuclear envelope (NE)/endoplasmic reticulum (ER) modulator that cooperates with the nuclear pore complex (NPC) biogenesis factors Brl1 and Brr6. How Apq12 executes these functions is unknown. Here, we identified a short amphipathic α-helix (AαH) in Apq12 that links the two transmembrane domains in the perinuclear space and has liposome-binding properties. Cells expressing an APQ12 (apq12-ah) version in which AαH is disrupted show NPC biogenesis and NE integrity defects, without impacting Apq12-ah topology or NE/ER localization. Overexpression of APQ12 but not apq12-ah triggers striking over-proliferation of the outer nuclear membrane (ONM)/ER and promotes accumulation of phosphatidic acid (PA) at the NE. Apq12 and Apq12-ah both associate with NPC biogenesis intermediates and removal of AαH increases both Brl1 levels and the interaction between Brl1 and Brr6. We conclude that the short amphipathic α-helix of Apq12 regulates the function of Brl1 and Brr6 and promotes PA accumulation at the NE possibly during NPC biogenesis.
- Published
- 2021
- Full Text
- View/download PDF
228. Characterization of nuclear pore complex targeting domains in Pom152 in Saccharomyces cerevisiae
- Author
-
Jacqueline T. Brown, Alexandra J. Haraczy, Christopher M. Wilhelm, and Kenneth D. Belanger
- Subjects
pom152 ,nuclear envelope ,nuclear pore complex ,nucleoporin ,Science ,Biology (General) ,QH301-705.5 - Abstract
Pom152 is a transmembrane protein within the nuclear pore complex (NPC) of fungi that is important for NPC assembly and structure. Pom152 is comprised of a short amino-terminal region that remains on the cytosolic side of the nuclear envelope (NE) and interacts with NPC proteins, a transmembrane domain, and a large, glycosylated carboxy-terminal domain within the NE lumen. Here we show that the N-terminal 200 amino acids of Pom152 that include only the amino-terminal and transmembrane regions are sufficient for localization to the NPC. Full-length, glycosylation-deficient, and truncated Pom152-GFP chimeras expressed in cells containing endogenous Pom152 localize to both NPCs and cortical endoplasmic reticulum (ER). Expression of Pom152-GFP fusions in pom152Δ cells results in detectable localization at only the NE by full-length and amino-terminal Pom152-GFP fusions, but continued retention at both the NE and ER for a chimera lacking just the carboxy-terminal 377 amino acids. Neither deletion of Pom152 nor its carboxy-terminal glycosylation sites altered the nuclear protein export rate of an Msn5/Kap142 protein cargo. These data narrow the Pom152 region sufficient for NPC localization and provide evidence that alterations in other domains may impact Pom152 targeting or affinity for the NPC.
- Published
- 2021
- Full Text
- View/download PDF
229. Mislocalization of Nucleocytoplasmic Transport Proteins in Human Huntington's Disease PSC-Derived Striatal Neurons.
- Author
-
Lange, Jenny, Wood-Kaczmar, Alison, Ali, Aneesa, Farag, Sahar, Ghosh, Rhia, Parker, Jennifer, Casey, Caroline, Uno, Yumiko, Kunugi, Akiyoshi, Ferretti, Patrizia, Andre, Ralph, and Tabrizi, Sarah J.
- Subjects
NUCLEAR transport ,HUNTINGTON disease ,CARRIER proteins ,NUCLEOCYTOPLASMIC interactions ,PROTEIN transport ,NEURONS - Abstract
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene (HTT). Disease progression is characterized by the loss of vulnerable neuronal populations within the striatum. A consistent phenotype across HD models is disruption of nucleocytoplasmic transport and nuclear pore complex (NPC) function. Here we demonstrate that high content imaging is a suitable method for detecting mislocalization of lamin-B1, RAN and RANGAP1 in striatal neuronal cultures thus allowing a robust, unbiased, highly powered approach to assay nuclear pore deficits. Furthermore, nuclear pore deficits extended to the selectively vulnerable DARPP32 + subpopulation neurons, but not to astrocytes. Striatal neuron cultures are further affected by changes in gene and protein expression of RAN, RANGAP1 and lamin-B1. Lowering total HTT using HTT- targeted anti-sense oligonucleotides partially restored gene expression, as well as subtly reducing mislocalization of proteins involved in nucleocytoplasmic transport. This suggests that mislocalization of RAN, RANGAP1 and lamin-B1 cannot be normalized by simply reducing expression of CAG-expanded HTT in the absence of healthy HTT protein. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
230. RNA transport from transcription to localized translation: a single molecule perspective.
- Author
-
Basyuk, Eugenia, Rage, Florence, and Bertrand, Edouard
- Subjects
MESSENGER RNA ,GENE expression ,GENETIC transcription ,NEUROLOGICAL disorders ,BIOLOGICAL transport ,NUCLEAR pore complex - Abstract
Transport of mRNAs is an important step of gene expression, which brings the genetic message from the DNA in the nucleus to a precise cytoplasmic location in a regulated fashion. Perturbation of this process can lead to pathologies such as developmental and neurological disorders. In this review, we discuss recent advances in the field of mRNA transport made using single molecule fluorescent imaging approaches. We present an overview of these approaches in fixed and live cells and their input in understanding the key steps of mRNA journey: transport across the nucleoplasm, export through the nuclear pores and delivery to its final cytoplasmic location. This review puts a particular emphasis on the coupling of mRNA transport with translation, such as localization-dependent translational regulation and translation-dependent mRNA localization. We also highlight the recently discovered translation factories, and how cellular and viral RNAs can hijack membrane transport systems to travel in the cytoplasm. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
231. Physics of the nuclear pore complex: Theory, modeling and experiment.
- Author
-
Hoogenboom, Bart W., Hough, Loren E., Lemke, Edward A., Lim, Roderick Y.H., Onck, Patrick R., and Zilman, Anton
- Subjects
- *
NUCLEAR physics , *NUCLEAR membranes , *CELL nuclei , *EUKARYOTIC cells , *BIOPHYSICS , *LENSES - Abstract
The hallmark of eukaryotic cells is the nucleus that contains the genome, enclosed by a physical barrier known as the nuclear envelope (NE). On the one hand, this compartmentalization endows the eukaryotic cells with high regulatory complexity and flexibility. On the other hand, it poses a tremendous logistic and energetic problem of transporting millions of molecules per second across the nuclear envelope, to facilitate their biological function in all compartments of the cell. Therefore, eukaryotes have evolved a molecular "nanomachine" known as the Nuclear Pore Complex (NPC). Embedded in the nuclear envelope, NPCs control and regulate all the bi-directional transport between the cell nucleus and the cytoplasm. NPCs combine high molecular specificity of transport with high throughput and speed, and are highly robust with respect to molecular noise and structural perturbations. Remarkably, the functional mechanisms of NPC transport are highly conserved among eukaryotes, from yeast to humans, despite significant differences in the molecular components among various species. The NPC is the largest macromolecular complex in the cell. Yet, despite its significant complexity, it has become clear that its principles of operation can be largely understood based on fundamental physical concepts, as have emerged from a combination of experimental methods of molecular cell biology, biophysics, nanoscience and theoretical and computational modeling. Indeed, many aspects of NPC function can be recapitulated in artificial mimics with a drastically reduced complexity compared to biological pores. We review the current physical understanding of the NPC architecture and function, with the focus on the critical analysis of experimental studies in cells and artificial NPC mimics through the lens of theoretical and computational models. We also discuss the connections between the emerging concepts of NPC operation and other areas of biophysics and bionanotechnology. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
232. The ESCRT-III protein VPS4, but not CHMP4B or CHMP2B, is pathologically increased in familial and sporadic ALS neuronal nuclei.
- Author
-
Coyne, Alyssa N. and Rothstein, Jeffrey D.
- Subjects
- *
NUCLEAR membranes , *AMYOTROPHIC lateral sclerosis , *NUCLEAR proteins , *HOMEOSTASIS , *NUCLEOPORINS , *PROTEINS , *PATHOGENESIS - Abstract
Nuclear pore complex injury has recently emerged as an early and significant contributor to familial and sporadic ALS disease pathogenesis. However, the molecular events leading to this pathological phenomenon characterized by the reduction of specific nucleoporins from neuronal nuclear pore complexes remain largely unknown. This is due in part to a lack of knowledge regarding the biological pathways and proteins underlying nuclear pore complex homeostasis specifically in human neurons. We have recently uncovered that aberrant nuclear accumulation of the ESCRT-III protein CHMP7 initiates nuclear pore complex in familial and sporadic ALS neurons. In yeast and non-neuronal mammalian cells, nuclear relocalization of CHMP7 has been shown to recruit the ESCRT-III proteins CHMP4B, CHMP2B, and VPS4 to facilitate nuclear pore complex and nuclear envelope repair and homeostasis. Here, using super resolution structured illumination microscopy, we find that neither CHMP4B nor CHMP2B are increased in ALS neuronal nuclei. In contrast, VPS4 expression is significantly increased in ALS neuronal nuclei prior to the emergence of nuclear pore injury in a CHMP7 dependent manner. However, unlike our prior CHMP7 knockdown studies, impaired VPS4 function does not mitigate alterations to the NPC and the integral transmembrane nucleoporin POM121. Collectively our data suggest that while alterations in VPS4 subcellular localization appear to be coincident with nuclear pore complex injury, therapeutic efforts to mitigate this pathogenic cascade should be targeted towards upstream events such as the nuclear accumulation of CHMP7 as we have previously described. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
233. Mutation of the nuclear pore complex component, aladin1, disrupts asymmetric cell division in Zea mays (maize).
- Author
-
Best, Norman B., Addo-Quaye, Charles, Bong-Suk Kim, Weil, Clifford F., Schulz, Burkhard, Johal, Guri, and Dilkes, Brian P.
- Subjects
- *
CORN , *CELL division , *AMINO acid residues , *ALLELES in plants , *STEM cells , *NONSENSE mutation - Abstract
The nuclear pore complex (NPC) regulates the movement of macromolecules between the nucleus and cytoplasm. Dysfunction of many components of the NPC results in human genetic diseases, including triple A syndrome (AAAS) as a result of mutations in ALADIN. Here, we report a nonsense mutation in the maize ortholog, aladin1 (ali1-1), at the orthologous amino acid residue of an AAAS allele from humans, alters plant stature, tassel architecture, and asymmetric divisions of subsidiary mother cells (SMCs). Crosses with the stronger nonsense allele ali1-2 identified complex allele interactions for plant height and aberrant SMC division. RNA-seq analysis of the ali1-1 mutant identified compensatory transcript accumulation for other NPC components as well as gene expression consequences consistent with conservation of ALADIN1 functions between humans and maize. These findings demonstrate that ALADIN1 is necessary for normal plant development, shoot architecture, and asymmetric cell division in maize. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
234. One Ring to Rule them All? Structural and Functional Diversity in the Nuclear Pore Complex.
- Author
-
Fernandez-Martinez, Javier and Rout, Michael P.
- Subjects
- *
DNA repair , *GENE expression , *MACROMOLECULES , *GENETIC regulation , *CYTOPLASM , *HISTONES - Abstract
The nuclear pore complex (NPC) is the massive protein assembly that regulates the transport of macromolecules between the nucleus and the cytoplasm. Recent breakthroughs have provided major insights into the structure of the NPC in different eukaryotes, revealing a previously unsuspected diversity of NPC architectures. In parallel, the NPC has been shown to be a key player in regulating essential nuclear processes such as chromatin organization, gene expression, and DNA repair. However, our knowledge of the NPC structure has not been able to address the molecular mechanisms underlying its regulatory roles. We discuss potential explanations, including the coexistence of alternative NPC architectures with specific functional roles. The NPC is a large protein assembly that regulates macromolecular transport between the nucleus and the cytoplasm, and acts as a regulatory platform for many other essential nuclear processes. NPC structural characterization has been challenging, but recent technical and methodological advances are advancing our understanding of NPC architecture. Structural analyses of the NPC in different organisms revealed that, although there is a common bauplan, a significant degree of variability is observed in the peripheral modules that build these NPCs. The multiple regulatory roles shown for the NPC suggest an even greater degree of NPC architectural diversity that has not yet been unveiled. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
235. Mislocalization of Nucleocytoplasmic Transport Proteins in Human Huntington’s Disease PSC-Derived Striatal Neurons
- Author
-
Jenny Lange, Alison Wood-Kaczmar, Aneesa Ali, Sahar Farag, Rhia Ghosh, Jennifer Parker, Caroline Casey, Yumiko Uno, Akiyoshi Kunugi, Patrizia Ferretti, Ralph Andre, and Sarah J. Tabrizi
- Subjects
Huntington’s disease ,nuclear pore complex ,striatal neurons ,antisense oligonucleotide ,pluripotent stem cell (PSC) ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene (HTT). Disease progression is characterized by the loss of vulnerable neuronal populations within the striatum. A consistent phenotype across HD models is disruption of nucleocytoplasmic transport and nuclear pore complex (NPC) function. Here we demonstrate that high content imaging is a suitable method for detecting mislocalization of lamin-B1, RAN and RANGAP1 in striatal neuronal cultures thus allowing a robust, unbiased, highly powered approach to assay nuclear pore deficits. Furthermore, nuclear pore deficits extended to the selectively vulnerable DARPP32 + subpopulation neurons, but not to astrocytes. Striatal neuron cultures are further affected by changes in gene and protein expression of RAN, RANGAP1 and lamin-B1. Lowering total HTT using HTT-targeted anti-sense oligonucleotides partially restored gene expression, as well as subtly reducing mislocalization of proteins involved in nucleocytoplasmic transport. This suggests that mislocalization of RAN, RANGAP1 and lamin-B1 cannot be normalized by simply reducing expression of CAG-expanded HTT in the absence of healthy HTT protein.
- Published
- 2021
- Full Text
- View/download PDF
236. RNA Nucleocytoplasmic Transport Defects in Neurodegenerative Diseases
- Author
-
Boehringer, Ashley, Bowser, Robert, Schousboe, Arne, Series Editor, Sattler, Rita, editor, and Donnelly, Christopher J., editor
- Published
- 2018
- Full Text
- View/download PDF
237. Changes in the Nuclear Envelope in Laminopathies
- Author
-
Dutta, Subarna, Bhattacharyya, Maitree, Sengupta, Kaushik, COHEN, IRUN R., Series Editor, LAJTHA, ABEL, Series Editor, LAMBRIS, JOHN D., Series Editor, PAOLETTI, RODOLFO, Series Editor, Rezaei, Nima, Series Editor, Chattopadhyay, Kausik, editor, and Basu, Subhash C., editor
- Published
- 2018
- Full Text
- View/download PDF
238. Transport and Communication Across the Nuclear Envelope
- Author
-
Huang, Jing and Cao, Yu, editor
- Published
- 2018
- Full Text
- View/download PDF
239. Caenorhabditis elegans Nuclear Pore Complexes in Genome Organization and Gene Expression
- Author
-
Muñoz-Jiménez, Celia María, Askjaer, Peter, and D’Angelo, Maximiliano, editor
- Published
- 2018
- Full Text
- View/download PDF
240. Nuclear Pore Complexes in DNA Repair and Telomere Maintenance
- Author
-
Simon, Marie-Noelle, Kalousi, Alkmini, Soutoglou, Evi, Géli, Vincent, Dargemont, Catherine, and D’Angelo, Maximiliano, editor
- Published
- 2018
- Full Text
- View/download PDF
241. Nuclear Pore Complexes in the Organization and Regulation of the Mammalian Genome
- Author
-
Raices, Marcela, D’Angelo, Maximiliano A., and D’Angelo, Maximiliano, editor
- Published
- 2018
- Full Text
- View/download PDF
242. Nuclear Pore Complex in Genome Organization and Gene Expression in Yeast
- Author
-
Randise-Hinchliff, Carlo, Brickner, Jason H., and D’Angelo, Maximiliano, editor
- Published
- 2018
- Full Text
- View/download PDF
243. Nucleoporin MOS7/Nup88 is required for mitosis in gametogenesis and seed development in Arabidopsis
- Author
-
Park, Guen Tae, Frost, Jennifer M, Park, Jin-Sup, Kim, Tae Ho, Lee, Jong Seob, Oh, Sung Aeong, Twell, David, Brooks, Janie Sue, Fischer, Robert L, and Choi, Yeonhee
- Subjects
Genetics ,1.1 Normal biological development and functioning ,Underpinning research ,Alleles ,Arabidopsis ,Arabidopsis Proteins ,Germ Cells ,Microtubules ,Mitosis ,Mutation ,Seeds ,microtubule dynamics ,gametogenesis ,nuclear pore complex ,mitosis ,plant reproduction - Abstract
Angiosperm reproduction is characterized by alternate diploid sporophytic and haploid gametophytic generations. Gametogenesis shares similarities with that of animals except for the formation of the gametophyte, whereby haploid cells undergo several rounds of postmeiotic mitosis to form gametes and the accessory cells required for successful reproduction. The mechanisms regulating gametophyte development in angiosperms are incompletely understood. Here, we show that the nucleoporin Nup88-homolog MOS7 (Modifier of Snc1,7) plays a crucial role in mitosis during both male and female gametophyte formation in Arabidopsis thaliana. Using a mutagenesis screen, we identify the mos7-5 mutant allele, which causes ovule and pollen abortion in MOS7/mos7-5 heterozygous plants, and preglobular stage embryonic lethality in homozygous mos7-5 seeds. During interphase, we show that MOS7 is localized to the nuclear membrane but, like many nucleoporins, is associated with the spindle apparatus during mitosis. We detect interactions between MOS7 and several nucleoporins known to control spindle dynamics, and find that in pollen from MOS7/mos7-5 heterozygotes, abortion is accompanied by a failure of spindle formation, cell fate specification, and phragmoplast activity. Most intriguingly, we show that following gamete formation by MOS7/mos7-5 heterozygous spores, inheritance of either the MOS7 or the mos7-5 allele by a given gamete does not correlate with its respective survival or abortion. Instead, we suggest a model whereby MOS7, which is highly expressed in the Pollen- and Megaspore Mother Cells, enacts a dosage-limiting effect on the gametes to enable their progression through subsequent mitoses.
- Published
- 2014
244. CLCC1 promotes hepatic neutral lipid flux and nuclear pore complex assembly.
- Subjects
NUCLEAR pore complex ,LIPIDS ,NUCLEAR membranes ,INTRACELLULAR space ,CELL anatomy - Abstract
A preprint abstract from biorxiv.org discusses the role of CLCC1 in promoting hepatic neutral lipid flux and nuclear pore complex assembly. Imbalances in lipid storage and secretion can lead to the accumulation of lipid droplets in hepatocytes, causing hepatic steatosis. Through CRISPR-Cas9 screens, researchers identified CLCC1 as a critical regulator of neutral lipid storage and secretion. Loss of CLCC1 resulted in the buildup of large lipid droplets in hepatoma cells and liver steatosis in mice. Additionally, CLCC1 was found to be homologous to yeast Brl1p and Brr6p, which are involved in nuclear pore complex assembly. The study suggests that CLCC1-mediated membrane remodeling plays a role in both hepatic neutral lipid flux and nuclear pore complex assembly. However, it is important to note that this preprint has not yet undergone peer review. [Extracted from the article]
- Published
- 2024
245. How a protein component of nuclear pore complexes regulates development of blood cells and may contribute to myeloid disorders.
- Subjects
NUCLEAR pore complex ,BLOOD cells ,NUCLEAR proteins ,PAROXYSMAL hemoglobinuria ,CELL anatomy ,NUCLEAR membranes ,ONCOLOGY - Abstract
A recent study published in Science Advances by researchers at Sanford Burnham Prebys has identified a protein component of nuclear pore complexes (NPCs) called Nup358 as a key player in the development of myeloid cells. Myeloid cells are critical immune cells responsible for fighting pathogens and their dysfunction can lead to myeloid disorders such as leukemias. The researchers found that when Nup358 was eliminated in a mouse model, there was a severe loss of mature myeloid cells and an abnormal accumulation of early progenitors of myeloid cells. This finding provides insights into how blood cells develop and how alterations in Nup358 may contribute to blood malignancies. The researchers hope that this research will contribute to the development of novel therapies targeting NPCs. [Extracted from the article]
- Published
- 2024
246. Nucleoporin NUP210L and BAF-paralogue BAF-L together ensure microtubule organization and nuclear integrity in spermatids (Updated May 29, 2024).
- Subjects
MICROTUBULES ,NUCLEAR pore complex ,NUCLEAR membranes ,DEVELOPMENTAL biology ,NUCLEOPROTEINS - Abstract
A preprint abstract from biorxiv.org discusses the role of two proteins, NUP210L and BAF-L, in ensuring microtubule organization and nuclear integrity in spermatids. These proteins are involved in various morphogenic processes during spermiogenesis, including nuclear elongation and chromatin compaction. While the individual inactivation of BAF-L or NUP210L in mice does not affect fertility, the double knockout of both proteins leads to spermatid arrest and mislocalization of nuclear pore complexes. The study suggests that the NPC array and chromatin play a crucial role in maintaining nuclear integrity during spermatid nuclear remodeling. However, it is important to note that this preprint has not undergone peer review. [Extracted from the article]
- Published
- 2024
247. Researchers from Francis Crick Institute Detail New Studies and Findings in the Area of Life Science (Structural Anisotropy Results In Mechano-directional Transport of Proteins Across Nuclear Pores).
- Subjects
LIFE sciences ,CARRIER proteins ,NUCLEAR proteins ,NUCLEAR pore complex ,PROTEIN transport - Abstract
A recent report from the Francis Crick Institute in London, United Kingdom, discusses new findings in the field of Life Science. The research focuses on the nuclear pore complex, which regulates the transport of proteins between the nucleus and cytoplasm of cells. The study reveals that the mechanical properties of proteins play a role in their transport across nuclear pores, with proteins containing locally soft regions exhibiting higher import rates. The researchers also developed a peptide tag that accelerates the import rate of stiff protein cargos. This research provides insights into the mechanisms of protein transport and nuclear mechanotransduction. [Extracted from the article]
- Published
- 2024
248. Mice lacking the nucleoporin NUP210L and BAF-paralogue BAF-L are infertile with disorganized manchette microtubules that invaginate the spermatid nucleus.
- Subjects
MICROTUBULES ,NUCLEAR pore complex ,NUCLEAR membranes ,MICE ,DEVELOPMENTAL biology - Abstract
According to a preprint abstract, researchers have discovered that two proteins, NUP210L and BAF-L, play a crucial role in the fertility of mice. While the inactivation of either protein alone did not affect fertility, mice lacking both proteins were infertile. These mice experienced arrested spermatid development, with mislocalized nuclear pore complexes and disorganized manchette microtubules. The researchers suggest that these proteins are important for maintaining nuclear integrity during spermatid nuclear remodeling. This research has not yet undergone peer review. [Extracted from the article]
- Published
- 2024
249. Research shows that 'softer' proteins can cross into the nucleus quicker.
- Subjects
SINGLE cell proteins ,NUCLEAR pore complex ,PROTEINS ,BIOPHYSICS ,NUCLEAR membranes - Abstract
Researchers at the Francis Crick Institute and King's College London have found that the softness or rigidity of proteins can affect how quickly they enter the nucleus of a cell. Proteins need to enter and exit the nucleus to perform various functions, such as regulating gene activity. The researchers discovered that proteins with a soft or flexible region near their nuclear-localization sequence were able to enter the nucleus more quickly. This finding could potentially be used to develop targeted drug delivery or increase the activity of specific genes. [Extracted from the article]
- Published
- 2024
250. Research Reports on Genetics from National Cancer Institute (NCI) Provide New Insights (Parallel genetic screens identify nuclear envelope homeostasis as a key determinant of telomere entanglement resolution in fission yeast).
- Subjects
NUCLEAR membranes ,GENETIC testing ,GENETICS ,NUCLEAR pore complex ,HOMEOSTASIS - Abstract
A recent research report from the National Cancer Institute (NCI) provides new insights into genetics. The study focuses on fission yeast and the role of nuclear envelope homeostasis in resolving telomere entanglement. The researchers conducted genetic screens and found that loss of genes encoding components of the nuclear pore complex (NPC) promotes telomere disentanglement and suppresses cold sensitivity. Additionally, genes involved in lipid metabolism were found to reverse the ability of certain mutations to suppress cold sensitivity. This research highlights the importance of nuclear envelope modulation and membrane fluidity in telomere entanglement resolution. [Extracted from the article]
- Published
- 2024
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