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Annual Review of Biochemistry Jun 2019The nuclear pore complex (NPC) serves as the sole bidirectional gateway of macromolecules in and out of the nucleus. Owing to its size and complexity (∼1,000 protein... (Review)
Review
The nuclear pore complex (NPC) serves as the sole bidirectional gateway of macromolecules in and out of the nucleus. Owing to its size and complexity (∼1,000 protein subunits, ∼110 MDa in humans), the NPC has remained one of the foremost challenges for structure determination. Structural studies have now provided atomic-resolution crystal structures of most nucleoporins. The acquisition of these structures, combined with biochemical reconstitution experiments, cross-linking mass spectrometry, and cryo-electron tomography, has facilitated the determination of the near-atomic overall architecture of the symmetric core of the human, fungal, and algal NPCs. Here, we discuss the insights gained from these new advances and outstanding issues regarding NPC structure and function. The powerful combination of bottom-up and top-down approaches toward determining the structure of the NPC offers a paradigm for uncovering the architectures of other complex biological machines to near-atomic resolution.
Topics: Active Transport, Cell Nucleus; Animals; Cell Nucleus; Cryoelectron Microscopy; Crystallography, X-Ray; Eukaryota; Humans; Models, Molecular; Nuclear Pore; Nuclear Pore Complex Proteins; Protein Conformation; Protein Subunits; RNA, Messenger
PubMed: 30883195
DOI: 10.1146/annurev-biochem-062917-011901 -
Cell Dec 2022Nuclear pore complexes (NPCs) are channels for nucleocytoplasmic transport of proteins and RNAs. However, it remains unclear whether composition, structure, and...
Nuclear pore complexes (NPCs) are channels for nucleocytoplasmic transport of proteins and RNAs. However, it remains unclear whether composition, structure, and permeability of NPCs dynamically change during the cleavage period of vertebrate embryos and affect embryonic development. Here, we report that the comprehensive NPC maturity (CNM) controls the onset of zygotic genome activation (ZGA) during zebrafish early embryogenesis. We show that more nucleoporin proteins are recruited to and assembled into NPCs with development, resulting in progressive increase of NPCs in size and complexity. Maternal transcription factors (TFs) transport into nuclei more efficiently with increasing CNM. Deficiency or dysfunction of Nup133 or Ahctf1/Elys impairs NPC assembly, maternal TFs nuclear transport, and ZGA onset, while nup133 overexpression promotes these processes. Therefore, CNM may act as a molecular timer for ZGA by controlling nuclear transport of maternal TFs that reach nuclear concentration thresholds at a given time to initiate ZGA.
Topics: Animals; Embryonic Development; Gene Expression Regulation, Developmental; Nuclear Pore; Nuclear Pore Complex Proteins; Transcription Factors; Zebrafish; Zygote; Genome
PubMed: 36493774
DOI: 10.1016/j.cell.2022.11.011 -
Microbiology (Reading, England) Mar 2022Pore-forming toxins (PFTs) are widely distributed in both Gram-negative and Gram-positive bacteria. PFTs can act as virulence factors that bacteria utilise in...
Pore-forming toxins (PFTs) are widely distributed in both Gram-negative and Gram-positive bacteria. PFTs can act as virulence factors that bacteria utilise in dissemination and host colonisation or, alternatively, they can be employed to compete with rival microbes in polymicrobial niches. PFTs transition from a soluble form to become membrane-embedded by undergoing large conformational changes. Once inserted, they perforate the membrane, causing uncontrolled efflux of ions and/or nutrients and dissipating the protonmotive force (PMF). In some instances, target cells intoxicated by PFTs display additional effects as part of the cellular response to pore formation. Significant progress has been made in the mechanistic description of pore formation for the different PFTs families, but in several cases a complete understanding of pore structure remains lacking. PFTs have evolved recognition mechanisms to bind specific receptors that define their host tropism, although this can be remarkably diverse even within the same family. Here we summarise the salient features of PFTs and highlight where additional research is necessary to fully understand the mechanism of pore formation by members of this diverse group of protein toxins.
Topics: Bacteria; Bacterial Toxins; Cell Membrane; Humans; Pore Forming Cytotoxic Proteins; Virulence Factors
PubMed: 35333704
DOI: 10.1099/mic.0.001154 -
Journal of Colloid and Interface Science Nov 2022The spontaneous imbibition of a liquid within porous media, known as wicking, can display uncommon features in textiles and yarns. Yarns exhibited step-wise wicking...
UNLABELLED
The spontaneous imbibition of a liquid within porous media, known as wicking, can display uncommon features in textiles and yarns. Yarns exhibited step-wise wicking dynamics not captured by current models.
HYPOTHESIS
Wicking dynamics in yarns not only depend on inter-fiber pore filling, but are mainly determined by the pore-to-pore transition processes and the structure of the pore network.
EXPERIMENTS
Fast X-ray tomographic microscopy is employed to reveal the pore scale processes and neutron radiography for the macroscopic water uptake in yarns. A semi-empirical pore network model is presented that employs the measured pore network topology and pore scale dynamics to reproduce the experimentally observed wicking dynamics in yarns.
FINDINGS
The yarn pore system is a sparse network of long and narrow pores that promotes step-wise uptake dynamics. Wicking in yarns displays fast pore filling events in the order of seconds and long waiting times between filling events up to several minutes while navigating the pore network. As main result, we find that a few filling events directly determine the macroscopic behavior of wicking in the sparse pore network of yarns. It is necessary to consider pore-to-pore transition waiting times and the pore network structure to explain the characteristics of wicking dynamics in yarns.
Topics: Capillary Action; Textiles
PubMed: 35714401
DOI: 10.1016/j.jcis.2022.04.060 -
Toxins Sep 2019Perforation of cellular membranes by pore-forming proteins can affect cell physiology, tissue integrity, or immune response. Since many pore-forming proteins are toxins... (Review)
Review
Perforation of cellular membranes by pore-forming proteins can affect cell physiology, tissue integrity, or immune response. Since many pore-forming proteins are toxins or highly potent virulence factors, they represent an attractive target for the development of molecules that neutralize their actions with high efficacy. There has been an assortment of inhibitors developed to specifically obstruct the activity of pore-forming proteins, in addition to vaccination and antibiotics that serve as a plausible treatment for the majority of diseases caused by bacterial infections. Here we review a wide range of potential inhibitors that can specifically and effectively block the activity of pore-forming proteins, from small molecules to more specific macromolecular systems, such as synthetic nanoparticles, antibodies, antibody mimetics, polyvalent inhibitors, and dominant negative mutants. We discuss their mechanism of inhibition, as well as advantages and disadvantages.
Topics: Animals; Cell Membrane; Humans; Pore Forming Cytotoxic Proteins
PubMed: 31546810
DOI: 10.3390/toxins11090545 -
Cell Stress Aug 2020Exocytosis is a universal process of eukaryotic cells, consisting of fusion between the vesicle and the plasma membranes, leading to the formation of a fusion pore, a... (Review)
Review
Exocytosis is a universal process of eukaryotic cells, consisting of fusion between the vesicle and the plasma membranes, leading to the formation of a fusion pore, a channel through which vesicle cargo exits into the extracellular space. In 1986, Rand and Parsegian proposed several stages to explain the nature of membrane fusion. Following stimulation, it starts with focused stress destabilization of membranes in contact, followed by the coalescence of two membrane surfaces. In the next fraction of a millisecond, restabilization of fused membranes is considered to occur to maintain the cell's integrity. This view predicted that once a fusion pore is formed, it must widen abruptly, irreversibly and fully, whereby the vesicle membrane completely integrates with and collapses into the plasma membrane (full fusion exocytosis). However, recent experimental evidence has revealed that once the fusion pore opens, it may also reversibly close (transient or kiss-and-run exocytosis). Here, we present a historical perspective on understanding the mechanisms that initiate the membrane merger and fusion pore formation. Next, post-fusion mechanisms that regulate fusion pore stability are considered, reflecting the state in which the forces of widening and constriction of fusion pores are balanced. Although the mechanisms generating these forces are unclear, they may involve lipids and proteins, including SNAREs, which play a role not only in the pre-fusion but also post-fusion stages of exocytosis. How molecules stabilize the fusion pore in the open state is key for a better understanding of fusion pore physiology in health and disease.
PubMed: 32908961
DOI: 10.15698/cst2020.09.230 -
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 -
Development (Cambridge, England) Dec 2020Nuclear pore complexes are multiprotein channels that span the nuclear envelope, which connects the nucleus to the cytoplasm. In addition to their main role in the... (Review)
Review
Nuclear pore complexes are multiprotein channels that span the nuclear envelope, which connects the nucleus to the cytoplasm. In addition to their main role in the regulation of nucleocytoplasmic molecule exchange, it has become evident that nuclear pore complexes and their components also have multiple transport-independent functions. In recent years, an increasing number of studies have reported the involvement of nuclear pore complex components in embryogenesis, cell differentiation and tissue-specific processes. Here, we review the findings that highlight the dynamic nature of nuclear pore complexes and their roles in many cell type-specific functions during development and tissue homeostasis.
Topics: Animals; Cell Differentiation; Cell Nucleus; Cytoplasm; Embryonic Development; Homeostasis; Humans; Nuclear Envelope; Nuclear Pore; Nuclear Pore Complex Proteins; Organ Specificity
PubMed: 33323374
DOI: 10.1242/dev.183442 -
Gels (Basel, Switzerland) Jul 2022This review discusses the most commonly employed methods for determining pore size and pore size distribution in bioaerogels. Aerogels are materials with high porosity... (Review)
Review
This review discusses the most commonly employed methods for determining pore size and pore size distribution in bioaerogels. Aerogels are materials with high porosity and large surface areas. Most of their pores are in the range of mesopores, between 2 and 50 nm. They often have smaller or larger pores, which presents a significant challenge in determining the exact mean pore size and pore size distribution in such materials. The precision and actual value of the pore size are of considerable importance since pore size and pore size distribution are among the main properties of aerogels and are often directly connected with the final application of those materials. However, many recently published papers discuss or present pore size as one of the essential achievements despite the misinterpretation or the wrong assignments of pore size determination. This review will help future research and publications evaluate the pore size of aerogels more precisely and discuss it correctly. The study covers methods such as gas adsorption, from which BJH and DFT models are often used, SEM, mercury porosimetry, and thermoporometry. The methods are described, and the results obtained are discussed. The following paper shows that there is still no precise method for determining pore size distribution or mean pore size in aerogels until now. Knowing that, it is expected that this field will evolve in the future.
PubMed: 35877523
DOI: 10.3390/gels8070438 -
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