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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 -
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 -
Frontiers in Molecular Biosciences 2021Pore forming proteins are a broad class of pathogenic proteins secreted by organisms as virulence factors due to their ability to form pores on the target cell membrane.... (Review)
Review
Pore forming proteins are a broad class of pathogenic proteins secreted by organisms as virulence factors due to their ability to form pores on the target cell membrane. Bacterial pore forming toxins (PFTs) belong to a subclass of pore forming proteins widely implicated in bacterial infections. Although the action of PFTs on target cells have been widely investigated, the underlying membrane response of lipids during membrane binding and pore formation has received less attention. With the advent of superresolution microscopy as well as the ability to carry out molecular dynamics (MD) simulations of the large protein membrane assemblies, novel microscopic insights on the pore forming mechanism have emerged over the last decade. In this review, we focus primarily on results collated in our laboratory which probe dynamic lipid reorganization induced in the plasma membrane during various stages of pore formation by two archetypal bacterial PFTs, cytolysin A (ClyA), an -toxin and listeriolysin O (LLO), a -toxin. The extent of lipid perturbation is dependent on both the secondary structure of the membrane inserted motifs of pore complex as well as the topological variations of the pore complex. Using confocal and superresolution stimulated emission depletion (STED) fluorescence correlation spectroscopy (FCS) and MD simulations, lipid diffusion, cholesterol reorganization and deviations from Brownian diffusion are correlated with the oligomeric state of the membrane bound protein as well as the underlying membrane composition. Deviations from free diffusion are typically observed at length scales below ∼130 nm to reveal the presence of local dynamical heterogeneities that emerge at the nanoscale-driven in part by preferential protein binding to cholesterol and domains present in the lipid membrane. Interrogating the lipid dynamics at the nanoscale allows us further differentiate between binding and pore formation of - and -PFTs to specific domains in the membrane. The molecular insights gained from the intricate coupling that occurs between proteins and membrane lipids and receptors during pore formation are expected to improve our understanding of the virulent action of PFTs.
PubMed: 34568431
DOI: 10.3389/fmolb.2021.737561 -
Cell Calcium Jan 2022In some lysosomal storage diseases (LSD) cholesterol accumulates in vesicles. Whether increased vesicle cholesterol affects vesicle fusion with the plasmalemma, where...
In some lysosomal storage diseases (LSD) cholesterol accumulates in vesicles. Whether increased vesicle cholesterol affects vesicle fusion with the plasmalemma, where the fusion pore, a channel between the vesicle lumen and the extracellular space, is formed, is unknown. Super-resolution microscopy revealed that after stimulation of exocytosis, pituitary lactotroph vesicles discharge cholesterol which transfers to the plasmalemma. Cholesterol depletion in lactotrophs and astrocytes, both exhibiting Ca-dependent exocytosis regulated by distinct Casources, evokes vesicle secretion. Although this treatment enhanced cytosolic levels of Ca in lactotrophs but decreased it in astrocytes, this indicates that cholesterol may well directly define the fusion pore. In an attempt to explain this mechanism, a new model of cholesterol-dependent fusion pore regulation is proposed. High-resolution membrane capacitance measurements, used to monitor fusion pore conductance, a parameter related to fusion pore diameter, confirm that at resting conditions reducing cholesterol increases, while enrichment with cholesterol decreases the conductance of the fusion pore. In resting fibroblasts, lacking the Npc1 protein, a cellular model of LSD in which cholesterol accumulates in vesicles, the fusion pore conductance is smaller than in controls, showing that vesicle cholesterol controls fusion pore and is relevant for pathophysiology of LSD.
Topics: Animals; Cell Membrane; Cholesterol; Exocytosis; Lactotrophs; Membrane Fusion; Rats; Rats, Wistar; Secretory Vesicles
PubMed: 34844123
DOI: 10.1016/j.ceca.2021.102503 -
Biochimica Et Biophysica Acta.... Apr 2021The cytoplasmic membrane is one of the most frequent cell targets of antimicrobial peptides (AMPs) and other biomolecules. Understanding the mechanism of action of AMPs... (Review)
Review
The cytoplasmic membrane is one of the most frequent cell targets of antimicrobial peptides (AMPs) and other biomolecules. Understanding the mechanism of action of AMPs at the molecular level is of utmost importance for designing of new membrane-specific molecules. In particular, the formation of pores, the structure and size of these pores are of great interest and require nanoscale resolution approaches, therefore, biophysical strategies are essential to achieve an understanding of these processes at this scale. In the case of membrane active peptides, pore formation or general membrane disruption is usually the last step before cell death, and so, pore size is generally directly associated to pore structure and stability and loss of cellular homeostasis, implicated in overall peptide activity. Up to date, there has not been a critical review discussing the methods that can be used specifically for estimating the pore dimensions induced by membrane active peptides. In this review we discuss the scope, relevance and popularity of the different biophysical techniques such as liposome leakage experiments, advanced microscopy, neutron or X-ray scattering, electrophysiological techniques and molecular dynamics studies, all of them useful for determining pore structure and dimension.
Topics: Lipid Bilayers; Liposomes; Molecular Dynamics Simulation; Pore Forming Cytotoxic Proteins
PubMed: 33465367
DOI: 10.1016/j.bbamem.2021.183551 -
The Journal of Biological Chemistry Jul 2021The nuclear pore complex is the sole gateway connecting the nucleoplasm and cytoplasm. In humans, the nuclear pore complex is one of the largest multiprotein assemblies... (Review)
Review
The nuclear pore complex is the sole gateway connecting the nucleoplasm and cytoplasm. In humans, the nuclear pore complex is one of the largest multiprotein assemblies in the cell, with a molecular mass of ∼110 MDa and consisting of 8 to 64 copies of about 34 different nuclear pore proteins, termed nucleoporins, for a total of 1000 subunits per pore. Trafficking events across the nuclear pore are mediated by nuclear transport receptors and are highly regulated. The nuclear pore complex is also used by several RNA viruses and almost all DNA viruses to access the host cell nucleoplasm for replication. Viruses hijack the nuclear pore complex, and nuclear transport receptors, to access the nucleoplasm where they replicate. In addition, the nuclear pore complex is used by the cell innate immune system, a network of signal transduction pathways that coordinates the first response to foreign invaders, including viruses and other pathogens. Several branches of this response depend on dynamic signaling events that involve the nuclear translocation of downstream signal transducers. Mounting evidence has shown that these signaling cascades, especially those steps that involve nucleocytoplasmic trafficking events, are targeted by viruses so that they can evade the innate immune system. This review summarizes how nuclear pore proteins and nuclear transport receptors contribute to the innate immune response and highlights how viruses manipulate this cellular machinery to favor infection. A comprehensive understanding of nuclear pore proteins in antiviral innate immunity will likely contribute to the development of new antiviral therapeutic strategies.
Topics: Active Transport, Cell Nucleus; DNA Viruses; Humans; Immune Evasion; Immunity, Innate; NF-kappa B; Nuclear Pore; Nuclear Pore Complex Proteins; RNA Viruses; Viral Nonstructural Proteins; Virus Diseases; Virus Replication
PubMed: 34097873
DOI: 10.1016/j.jbc.2021.100856 -
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 -
Frontiers in Plant Science 2022Pore structure is a key determinant of soil functioning, and both root growth and activity of soil fauna are modified by and interact with pore structure in multiple...
Pore structure is a key determinant of soil functioning, and both root growth and activity of soil fauna are modified by and interact with pore structure in multiple ways. Cover cropping is a rapidly growing popular strategy for improving agricultural sustainability, including improvements in pore structure. However, since cover crop species encompass a variety of contrasting root architectures, they can have disparate effects on formation of soil pores and their characteristics, thus on the pore structure formation. Moreover, utilization of the existing pore systems and its modification by new root growth, in conjunction with soil fauna activity, can also vary by cover crop species, affecting the dynamics of biopores (creation and demolition). The objectives of this study were (i) to quantify the influence of 5 cover crop species on formation and size distribution of soil macropores (>36 μm Ø); (ii) to explore the changes in the originally developed pore architecture after an additional season of cover crop growth; and (iii) to assess the relative contributions of plant roots and soil fauna to fate and modifications of biopores. Intact soil cores were taken from 5 to 10 cm depth after one season of cover crop growth, followed by X-ray computed micro-tomography (CT) characterization, and then, the cores were reburied for a second root growing period of cover crops to explore subsequent changes in pore characteristics with the second CT scanning. Our data suggest that interactions of soil fauna and roots with pore structure changed over time. While in the first season, large biopores were created at the expense of small pores, in the second year these biopores were reused or destroyed by the creation of new ones through earthworm activities and large root growth. In addition, the creation of large biopores (>0.5 mm) increased total macroporosity. During the second root growing period, these large sized macropores, however, are reduced in size again through the action of soil fauna smaller than earthworms, suggesting a highly dynamic equilibrium. Different effects of cover crops on pore structure mainly arise from their differences in root volume, mean diameter as well as their reuse of existing macropores.
PubMed: 36160999
DOI: 10.3389/fpls.2022.928569 -
Journal of Colloid and Interface Science Mar 2022Imbibition of a fluid into a porous material involves the invasion of a wetting fluid in the pore space through piston-like displacement, film and corner flow, snap-off...
HYPOTHESIS
Imbibition of a fluid into a porous material involves the invasion of a wetting fluid in the pore space through piston-like displacement, film and corner flow, snap-off and pore bypassing. These processes have been studied extensively in two-dimensional (2D) porous systems; however, their relevance to three-dimensional (3D) natural porous media is poorly understood. Here, we investigate these pore-scale processes in a natural rock sample using time-resolved 3D (i.e., four-dimensional or 4D) X-ray imaging.
EXPERIMENTS
We performed a capillary-controlled drainage-imbibition experiment on an initially brine-saturated carbonate rock sample. The sample was imaged continuously during imbibition using 4D X-ray imaging to visualize and analyze fluid displacement and snap-off processes at the pore-scale.
FINDINGS
We discover a new type of snap-off that occurs in pores, resulting in the entrapment of a small portion of the non-wetting phase in pore corners. This contrasts with previously-observed snap-off in throats which traps the non-wetting phase in pore centers. We relate the new type of pore-snap-off to the pinning of fluid-fluid interfaces at rough surfaces, creating contact angles close to 90°. Subsequently, we provide correlations for displacement events as a function of pore-throat geometry. Our findings indicate that having a small throat does not necessarily favor snap-off: the key criterion is the throat radius in relation to the pore radius involved in a displacement event, captured by the aspect ratio.
PubMed: 34902675
DOI: 10.1016/j.jcis.2021.11.109 -
Materials (Basel, Switzerland) Mar 2021This paper aims to develop frost-resistant concretes, and investigate their pore structures and freeze-thaw damage mechanism. The frost-resistant concrete mixtures are...
This paper aims to develop frost-resistant concretes, and investigate their pore structures and freeze-thaw damage mechanism. The frost-resistant concrete mixtures are designed by using rubber particles and nano-SiO to partially replace sands. The chord lengths, specific surface areas, contents and spacing coefficients of the pores in the designed concretes are measured and analyzed. The results show that concrete mixture incorporated with 5% silanized rubber and 3% nanosilica shows good synergetic effect by considering both mass loss and relative dynamic modulus of elasticity (RDME). The freeze-thaw damage degree of the concrete could be reduced by adding high elastic rubber particles, due to filling and constraining pores, and resulting in better uniform pore distribution and smaller pore spacing coefficient. Furthermore, the correlations between frost resistance and pore are analyzed and proposed.
PubMed: 33801516
DOI: 10.3390/ma14051170