-
Frontiers in Bioscience (Landmark... Dec 2023Nuclear pore complexes (NPCs) are intricate intracellular structures composed of approximately 30 nuclear pore proteins (NUPs) that regulate the transport of materials... (Review)
Review
Nuclear pore complexes (NPCs) are intricate intracellular structures composed of approximately 30 nuclear pore proteins (NUPs) that regulate the transport of materials between the nucleus and cytoplasm in eukaryotic cells. The heart is a crucial organ for sustaining the vital functions of the body, pumping blood rich in nutrients and energy to all organs and tissues. Recent studies have shown that NPCs play pivotal roles not only in normal cardiac physiological processes such as myocardial cell proliferation and differentiation but also in various pathological processes such as ischemic and hypoxic myocardial injury. Due to their mass and complicated nature, the structures of NPCs have been challenging to identify by the scientific community. With the development of cryo-electron microscopy and advanced sampling techniques, researchers have made significant progress in understanding the structures of NPCs. This review aims to summarize the latest research on the structural aspects of NPCs and their roles in cardiac physiology and pathology, increase the understanding of the intricate mechanisms of NPC actions, provide valuable insights into the pathogenesis of heart diseases and describe the development of potential novel therapeutic strategies.
Topics: Nuclear Pore Complex Proteins; Active Transport, Cell Nucleus; Cryoelectron Microscopy; Nuclear Pore; Cytoplasm
PubMed: 38179752
DOI: 10.31083/j.fbl2812350 -
DNA Repair Oct 2023The nuclear pore complexes (NPCs), one of the hallmarks of eukaryotic nuclei, allow selective transport of macromolecules between the cytoplasm and the nucleus. Besides... (Review)
Review
The nuclear pore complexes (NPCs), one of the hallmarks of eukaryotic nuclei, allow selective transport of macromolecules between the cytoplasm and the nucleus. Besides this canonical function, an increasing number of additional roles have been attributed to the NPCs and their constituents, the nucleoporins. Here we review recent insights into the mechanisms by which NPCs and nucleoporins affect transcription and DNA repair in metazoans. In the first part, we discuss how gene expression can be affected by the localization of genome-nucleoporin interactions at pores or "off-pores", by the role of nucleoporins in chromatin organization at different scales, or by the physical properties of nucleoporins. In the second part, we review the contribution of NPCs to genome stability, including transport-dependent and -independent functions and the role of positioning at NPCs in the repair of heterochromatic breaks and the regulation of replication stress.
Topics: Animals; Nuclear Pore; Nuclear Pore Complex Proteins; Gene Expression Regulation; Cytoplasm; Genomic Instability
PubMed: 37696111
DOI: 10.1016/j.dnarep.2023.103565 -
FEBS Letters Oct 2023One of the remarkable features of eukaryotes is the nucleus, delimited by the nuclear envelope (NE), a complex structure and home to the nuclear lamina and nuclear pore... (Review)
Review
One of the remarkable features of eukaryotes is the nucleus, delimited by the nuclear envelope (NE), a complex structure and home to the nuclear lamina and nuclear pore complex (NPC). For decades, these structures were believed to be mainly architectural elements and, in the case of the NPC, simply facilitating nucleocytoplasmic trafficking. More recently, the critical roles of the lamina, NPC and other NE constituents in genome organisation, maintaining chromosomal domains and regulating gene expression have been recognised. Importantly, mutations in genes encoding lamina and NPC components lead to pathogenesis in humans, while pathogenic protozoa disrupt the progression of normal development and expression of pathogenesis-related genes. Here, we review features of the lamina and NPC across eukaryotes and discuss how these elements are structured in trypanosomes, protozoa of high medical and veterinary importance, highlighting lineage-specific and conserved aspects of nuclear organisation.
Topics: Humans; Active Transport, Cell Nucleus; Nuclear Pore Complex Proteins; Nuclear Envelope; Nuclear Pore; Trypanosoma
PubMed: 37789516
DOI: 10.1002/1873-3468.14747 -
Biomedicine & Pharmacotherapy =... Sep 2023Recent studies have found that receptor interacting protein kinase 3 (RIPK3) can mediate CaMK Ⅱ phosphorylation and oxidation, open mitochondrial permeability... (Review)
Review
Recent studies have found that receptor interacting protein kinase 3 (RIPK3) can mediate CaMK Ⅱ phosphorylation and oxidation, open mitochondrial permeability transition pore (mPTP), and induce myocardial necroptosis. The increased expression or phosphorylation of RIPK3 is one of the important markers of necroptosis; Inhibition of CaMK Ⅱ phosphorylation or oxidation significantly reduces RIPK3 mediated myocardial necroptosis; Studies have shown that necroptosis plays an important role in the occurrence and development of cardiovascular diseases; Using the selective inhibitor GSK '872 of RIPK3 can effectively inhibit the occurrence and development of cardiovascular diseases, and can reverse cardiovascular and cardiac dysfunction caused by overexpression of RIPK3. In this review, we provide a brief overview of the current knowledge on RIPK3 in mediating necroptosis, inflammatory response, and oxidative stress, and discussed the role of RIPK3 in cardiovascular diseases such as atherosclerosis, myocardial ischaemia, myocardial infarction, and heart failure.
Topics: Humans; Cardiovascular Diseases; Myocardial Infarction; Mitochondrial Permeability Transition Pore; Phosphorylation; Protein Kinases
PubMed: 37329707
DOI: 10.1016/j.biopha.2023.114696 -
The EMBO Journal Jul 2023Nucleoporins (Nups) assemble nuclear pores that form the permeability barrier between nucleoplasm and cytoplasm. Nucleoporins also localize in cytoplasmic foci proposed...
Nucleoporins (Nups) assemble nuclear pores that form the permeability barrier between nucleoplasm and cytoplasm. Nucleoporins also localize in cytoplasmic foci proposed to function as pore pre-assembly intermediates. Here, we characterize the composition and incidence of cytoplasmic Nup foci in an intact animal, C. elegans. We find that, in young non-stressed animals, Nup foci only appear in developing sperm, oocytes and embryos, tissues that express high levels of nucleoporins. The foci are condensates of highly cohesive FG repeat-containing nucleoporins (FG-Nups), which are maintained near their solubility limit in the cytoplasm by posttranslational modifications and chaperone activity. Only a minor fraction of FG-Nup molecules concentrate in Nup foci, which dissolve during M phase and are dispensable for nuclear pore assembly. Nucleoporin condensation is enhanced by stress and advancing age, and overexpression of a single FG-Nup in post-mitotic neurons is sufficient to induce ectopic condensation and organismal paralysis. We speculate that Nup foci are non-essential and potentially toxic condensates whose assembly is actively suppressed in healthy cells.
Topics: Male; Animals; Nuclear Pore Complex Proteins; Nuclear Pore; Caenorhabditis elegans; Semen; Cell Nucleus; Active Transport, Cell Nucleus
PubMed: 37254647
DOI: 10.15252/embj.2022112987 -
EMBO Reports Sep 2023During mitotic entry of vertebrate cells, nuclear pore complexes (NPCs) are rapidly disintegrated. NPC disassembly is initiated by hyperphosphorylation of linker...
During mitotic entry of vertebrate cells, nuclear pore complexes (NPCs) are rapidly disintegrated. NPC disassembly is initiated by hyperphosphorylation of linker nucleoporins (Nups), which leads to the dissociation of FG repeat Nups and relaxation of the nuclear permeability barrier. However, less is known about disintegration of the huge nuclear and cytoplasmic rings, which are formed by annular assemblies of Y-complexes that are dissociated from NPCs as intact units. Surprisingly, we observe that Y-complex Nups display slower dissociation kinetics compared with other Nups during in vitro NPC disassembly, indicating a mechanistic difference in the disintegration of Y-based rings. Intriguingly, biochemical experiments reveal that a fraction of Y-complexes remains associated with mitotic ER membranes, supporting recent microscopic observations. Visualization of mitotic Y-complexes by super-resolution microscopy demonstrates that they form two classes of higher order assemblies: large clusters at kinetochores and small, focal ER-associated assemblies. These, however, lack features qualifying them as persisting ring-shaped subassemblies previously proposed to serve as structural templates for NPC reassembly during mitotic exit, which helps to refine current models of nuclear reassembly.
Topics: Microscopy; Mitosis; Nuclear Pore; Cell Nucleus; Nuclear Pore Complex Proteins
PubMed: 37469276
DOI: 10.15252/embr.202356766 -
Nature Feb 2024HIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the...
HIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the nucleus. Remarkably, the intact HIV capsid is more than 1,000 times larger than the size limit prescribed by the diffusion barrier of the nuclear pore. This barrier in the central channel of the nuclear pore is composed of intrinsically disordered nucleoporin domains enriched in phenylalanine-glycine (FG) dipeptides. Through multivalent FG interactions, cellular karyopherins and their bound cargoes solubilize in this phase to drive nucleocytoplasmic transport. By performing an in vitro dissection of the nuclear pore complex, we show that a pocket on the surface of the HIV capsid similarly interacts with FG motifs from multiple nucleoporins and that this interaction licences capsids to penetrate FG-nucleoporin condensates. This karyopherin mimicry model addresses a key conceptual challenge for the role of the HIV capsid in nuclear entry and offers an explanation as to how an exogenous entity much larger than any known cellular cargo may be able to non-destructively breach the nuclear envelope.
Topics: Humans; Active Transport, Cell Nucleus; Capsid Proteins; Diffusion; Dipeptides; Glycine; HIV; In Vitro Techniques; Intrinsically Disordered Proteins; Karyopherins; Molecular Mimicry; Nuclear Pore; Nuclear Pore Complex Proteins; Permeability; Phenylalanine; Solubility; Virus Internalization; Capsid
PubMed: 38267582
DOI: 10.1038/s41586-023-06969-7 -
Synthesis of Pore-Size-Tunable Porous Silica Particles and Their Effects on Dental Resin Composites.Biomolecules Aug 2023The filler/resin matrix interface interaction plays a vital role in the properties of dental resin composites (DRCs). Porous particles are promising fillers due to their...
The filler/resin matrix interface interaction plays a vital role in the properties of dental resin composites (DRCs). Porous particles are promising fillers due to their potential in constructing micromechanical interlocking at filler/resin matrix interfaces, therefore improving the properties of the resulting DRCs, where the pore size is significantly important. However, how to control the pore size of porous particles via a simple synthesis method is still a challenge, and how their pore sizes affect the properties of resulting DRCs has not been studied. In this study, porous silica (DPS) with a dendritic structure and an adjustable pore size was synthesized by changing the amounts of catalyst in the initial microemulsion. These synthesized DPS particles were directly used as unimodal fillers and mixed with a resin matrix to formulate DRCs. The results showed that the DPS pore size affects the properties of DRCs, especially the mechanical property. Among various DPS particles with different pore sizes, DPS6 resulted in 19.5% and 31.4% improvement in flexural strength, and 24.4% and 30.7% enhancement in compression strength, respectively, compared to DPS1 and DPS9. These DPS particles could help to design novel dental restorative materials and have promising applications in biomedicine, catalysis, and adsorption.
Topics: Porosity; Adsorption; Catalysis; Excipients; Silicon Dioxide; Resins, Synthetic
PubMed: 37759690
DOI: 10.3390/biom13091290 -
Micromachines Dec 2023To adsorb and remove formaldehyde, which is a harmful volatile organic chemical (VOC) detected indoors, an alkylamine was introduced into the substrate as a formaldehyde...
To adsorb and remove formaldehyde, which is a harmful volatile organic chemical (VOC) detected indoors, an alkylamine was introduced into the substrate as a formaldehyde adsorbent. In this study, Tetraethylenepentaamine (TEPA) was introduced into the mesoporous silica using the amine impregnation method. Since the impregnated alkylamine can block the pores of the silica substrate, the pore size and pore volume are very important factors for its use as a substrate for an adsorbent. Focusing on the substrate's pore properties, Santa Barbara Amorphous-15 (SBA-15) was chosen as a conventional one-dimensional pore-structured mesoporous silica, and dendritic mesoporous silica (DMS) as a three-dimensional pore-structured mesoporous silica. To 1 g each of silica substrate DMS and SBA-15, 0, 0.5, 1.5, and 2.5 g of TEPA were introduced. A fixed concentration and amount of formaldehyde gas was flowed through the adsorbent and then the adsorbent was changed to the 2,4-Dinitrophenylhydrazine (2,4-DNPH) cartridge to adsorb the remaining formaldehyde. According to the methods recommended by the World Health Organization (WHO) and National Institute for Occupational Safety & Health (NIOSH), the formaldehyde captured by 2,4-DNPH was analyzed using high-performance liquid chromatography (HPLC). A comparison of DMS and SBA-15 in the amine impregnation method shows that not only surface area, but also large pore size and high pore volume, contribute to the formaldehyde adsorption ability.
PubMed: 38258149
DOI: 10.3390/mi15010030 -
Frontiers in Cell and Developmental... 2023
PubMed: 38125874
DOI: 10.3389/fcell.2023.1340745