Dynamic rearrangement of nucleoporins during fungal "open" mitosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Theisen U
PROVIDER: S-EPMC2262998 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Successful cell division involves highly regulated transcriptional and post-transcriptional control. The RNA poly(A) tail represents an important layer of RNA post-transcriptional regulation. Previous TAIL-seq analysis of S phase and M phase poly(A) tail information showed that only a small number of genes showed more than 2-fold change in their poly(A) tail length between the two cell cycle stages. In addition, the changes in poly(A) tail length between these two stages showed minimal impact on the translation of the genes as long as the poly(A) tails were longer than 20 nt. Therefore, the significance of poly(A) tail dynamics during the cell cycle remains largely unknown. Here, by re-analyzing the S phase and M phase TAIL-seq data, we uncovered an interesting global dynamics of RNA poly(A) tails in terms of their terminal modifications, implying global RNA regulation between mitotic cell cycles through poly(A) tail terminal modifications.
| S-EPMC7415821 | biostudies-literature
Project description:Emerin, MAN1, and LAP2 are integral membrane proteins of the vertebrate nuclear envelope. They share a 43-residue N-terminal motif termed the LEM domain. We found three putative LEM domain genes in Caenorhabditis elegans, designated emr-1, lem-2, and lem-3. We analyzed emr-l, which encodes Ce-emerin, and lem-2, which encodes Ce-MAN1. Ce-emerin and Ce-MAN1 migrate on SDS-PAGE as 17- and 52-kDa proteins, respectively. Based on their biochemical extraction properties and immunolocalization, both Ce-emerin and Ce-MAN1 are integral membrane proteins localized at the nuclear envelope. We used antibodies against Ce-MAN1, Ce-emerin, nucleoporins, and Ce-lamin to determine the timing of nuclear envelope breakdown during mitosis in C. elegans. The C. elegans nuclear envelope disassembles very late compared with vertebrates and Drosophila. The nuclear membranes remained intact everywhere except near spindle poles during metaphase and early anaphase, fully disassembling only during mid-late anaphase. Disassembly of pore complexes, and to a lesser extent the lamina, depended on embryo age: pore complexes were absent during metaphase in >30-cell embryos but existed until anaphase in 2- to 24-cell embryos. Intranuclear mRNA splicing factors disassembled after prophase. The timing of nuclear disassembly in C. elegans is novel and may reflect its evolutionary position between unicellular and more complex eukaryotes.
| S-EPMC14977 | biostudies-literature
Project description:Transcription factor Oct1 regulates multiple cellular processes. It is known to be phosphorylated during the cell cycle and by stress, however the upstream kinases and downstream consequences are not well understood. One of these modified forms, phosphorylated at S335, lacks the ability to bind DNA. Other modification states besides phosphorylation have not been described.We show that Oct1 is phosphorylated at S335 in the Oct1 DNA binding domain during M-phase by the NIMA-related kinase Nek6. Phospho-Oct1 is also ubiquitinated. Phosphorylation excludes Oct1 from mitotic chromatin. Instead, Oct1(pS335) concentrates at centrosomes, mitotic spindle poles, kinetochores and the midbody. Oct1 siRNA knockdown diminishes the signal at these locations. Both Oct1 ablation and overexpression result in abnormal mitoses. S335 is important for the overexpression phenotype, implicating this residue in mitotic regulation. Oct1 depletion causes defects in spindle morphogenesis in Xenopus egg extracts, establishing a mitosis-specific function of Oct1. Oct1 colocalizes with lamin B1 at the spindle poles and midbody. At the midbody, both proteins are mutually required to correctly localize the other. We show that phospho-Oct1 is modified late in mitosis by non-canonical K11-linked polyubiquitin chains. Ubiquitination requires the anaphase-promoting complex, and we further show that the anaphase-promoting complex large subunit APC1 and Oct1(pS335) interact.These findings reveal mechanistic coupling between Oct1 phosphorylation and ubquitination during mitotic progression, and a role for Oct1 in mitosis.
| S-EPMC3163677 | biostudies-literature
Project description:The most polymorphic gene family in P. falciparum is the ∼60 var genes distributed across parasite chromosomes, both in the subtelomeres and in internal regions. They encode hypervariable surface proteins known as P. falciparum erythrocyte membrane protein 1 (PfEMP1) that are critical for pathogenesis and immune evasion in Plasmodium falciparum. How var gene sequence diversity is generated is not currently completely understood. To address this, we constructed large clone trees and performed whole genome sequence analysis to study the generation of novel var gene sequences in asexually replicating parasites. While single nucleotide polymorphisms (SNPs) were scattered across the genome, structural variants (deletions, duplications, translocations) were focused in and around var genes, with considerable variation in frequency between strains. Analysis of more than 100 recombination events involving var exon 1 revealed that the average nucleotide sequence identity of two recombining exons was only 63% (range: 52.7-72.4%) yet the crossovers were error-free and occurred in such a way that the resulting sequence was in frame and domain architecture was preserved. Var exon 1, which encodes the immunologically exposed part of the protein, recombined in up to 0.2% of infected erythrocytes in vitro per life cycle. The high rate of var exon 1 recombination indicates that millions of new antigenic structures could potentially be generated each day in a single infected individual. We propose a model whereby var gene sequence polymorphism is mainly generated during the asexual part of the life cycle.
| S-EPMC4270465 | biostudies-literature
Project description:The assembly of microtubules inside the cell is controlled both spatially and temporally. During mitosis, microtubule assembly must be activated locally at the nascent spindle region for mitotic spindle assembly to occur efficiently. In this paper, we report that mitotic spindle components, such as free tubulin subunits, accumulated in the nascent spindle region, independent of spindle formation in the Caenorhabditis elegans embryo. This accumulation coincided with nuclear envelope permeabilization, suggesting that permeabilization might trigger the accumulation. When permeabilization was induced earlier by knockdown of lamin, tubulin also accumulated earlier. The boundaries of the region of accumulation coincided with the remnant nuclear envelope, which remains after nuclear envelope breakdown in cells that undergo semi-open mitosis, such as those of C. elegans. Ran, a small GTPase protein, was required for tubulin accumulation. Fluorescence recovery after photobleaching analysis revealed that the accumulation was accompanied by an increase in the immobile fraction of free tubulin inside the remnant nuclear envelope. We propose that this newly identified mechanism of accumulation of free tubulin-and probably of other molecules-at the nascent spindle region contributes to efficient assembly of the mitotic spindle in the C. elegans embryo.
| S-EPMC3338436 | biostudies-literature
Project description:Although mammals are thought to lose their capacity to regenerate heart muscle shortly after birth, embryonic and neonatal cardiomyocytes in mammals are hyperplastic. During proliferation these cells need to selectively disassemble their myofibrils for successful cytokinesis. The mechanism of sarcomere disassembly is, however, not understood. To study this, we performed a series of immunofluorescence studies of multiple sarcomeric proteins in proliferating neonatal rat ventricular myocytes and correlated these observations with biochemical changes at different cell cycle stages. During myocyte mitosis, α-actinin and titin were disassembled as early as prometaphase. α-actinin (representing the sarcomeric Z-disk) disassembly precedes that of titin (M-line), suggesting that titin disassembly occurs secondary to the collapse of the Z-disk. Sarcomere disassembly was concurrent with the dissolution of the nuclear envelope. Inhibitors of several intracellular proteases could not block the disassembly of α-actinin or titin. There was a dramatic increase in both cytosolic (soluble) and sarcomeric α-actinin during mitosis, and cytosolic α-actinin exhibited decreased phosphorylation compared to sarcomeric α-actinin. Inhibition of cyclin-dependent kinase 1 (CDK1) induced the quick reassembly of the sarcomere. Sarcomere dis- and re-assembly in cardiomyocyte mitosis is CDK1-dependent and features dynamic differential post-translational modifications of sarcomeric and cytosolic α-actinin.
| S-EPMC4467976 | biostudies-literature
Project description:The cytoplasmic localization of Nuclear Receptor Coactivator 4 (NcoA4), also referred to as androgen receptor associated protein 70 (ARA70), indicates it may possess activities in addition to its role within the nucleus as a transcriptional enhancer. Towards identifying novel functions of NcoA4, we performed an in silico analysis of its amino acid sequence to identify potential functional domains and related proteins, and examined its subcellular distribution throughout the cell cycle. NcoA4 has no known or predicted functional or structural domains with the exception of an LxxLL and FxxLF nuclear receptor interaction motif and an N-terminal putative coiled-coil domain. Phylogenetic analysis indicated that NcoA4 has no paralogs and that a region referred to as ARA70-I family domain, located within the N-terminus and overlapping with the coiled-coil domain, is evolutionarily conserved in metazoans ranging from cnidarians to mammals. An adjacent conserved region, designated ARA70-II family domain, with no significant sequence similarity to the ARA70-I domain, is restricted to vertebrates. We demonstrate NcoA4 co-localizes with microtubules and microtubule organizing centers during prophase. Strong NcoA4 accumulation at the centrosomes was detected during interphase and telophase, with decreased levels at metaphase and anaphase. NcoA4 co-localized with tubulin and acetylated tubulin to the mitotic spindles during metaphase and anaphase, and to midbodies during telophase. Consistent with these observations, we demonstrated an interaction between NcoA4 and α-tubulin. Co-localization was not observed with microfilaments. These findings indicate a dynamic distribution of NcoA4 with components of the mitotic apparatus that is consistent with a potential non-transcriptional regulatory function(s) during cell division, which may be evolutionarily conserved.
| S-EPMC3144208 | biostudies-literature
Project description:Before chromosomes segregate into daughter cells, they align at the mitotic spindle equator, a process known as chromosome congression. Centromere-associated protein E (CENP-E)/Kinesin-7 is a microtubule plus-end-directed kinetochore motor required for congression of pole-proximal chromosomes. Because the plus-ends of many astral microtubules in the spindle point to the cell cortex, it remains unknown how CENP-E guides pole-proximal chromosomes specifically toward the equator. We found that congression of pole-proximal chromosomes depended on specific posttranslational detyrosination of spindle microtubules that point to the equator. In vitro reconstitution experiments demonstrated that CENP-E-dependent transport was strongly enhanced on detyrosinated microtubules. Blocking tubulin tyrosination in cells caused ubiquitous detyrosination of spindle microtubules, and CENP-E transported chromosomes away from spindle poles in random directions. Thus, CENP-E-driven chromosome congression is guided by microtubule detyrosination.
| S-EPMC4506776 | biostudies-literature
Project description:The nuclear envelope is a physical barrier between the nucleus and cytoplasm and, as such, separates the mechanisms of transcription from translation. This compartmentalization of eukaryotic cells allows spatial regulation of gene expression; however, it also necessitates a mechanism for transport between the nucleus and cytoplasm. Macromolecular trafficking of protein and RNA occurs exclusively through nuclear pore complexes (NPCs), specialized channels spanning the nuclear envelope. A novel family of NPC proteins, the FG-nucleoporins (FG-Nups), coordinates and potentially regulates NPC translocation. The extensive repeats of phenylalanine-glycine (FG) in each FG-Nup directly bind to shuttling transport receptors moving through the NPC. In addition, FG-Nups are essential components of the nuclear permeability barrier. In this review, we discuss the structural features, cellular functions, and evolutionary conservation of the FG-Nups.
| S-EPMC2794212 | biostudies-literature
Project description:Decline in ovarian reserve with aging is associated with reduced fertility and the development of metabolic abnormalities. Once mitochondrial homeostasis is imbalanced, it may lead to poor reproductive cell quality and aging. However, Phosphoglycerate translocase 5 (PGAM5), located in the mitochondrial membrane, is associated with necroptosis, apoptosis, and mitophagy, although the underlying mechanisms associated with ovarian aging remain unknown. Therefore, we attempted to uncover whether the high phosphoglycerate mutant enzyme family member 5 (PGAM5) expression is associated with female infertility in cumulus cells, and aims to find out the underlying mechanism of action of PGAM5. We found that PGAM5 is highly expressed and positively associated with aging, and has the potential to help maintain and regulate mitochondrial dynamics and metabolic reprogramming in aging granulosa cells, ovaries of aged female mice, and elderly patients. PGAM5 undergoes activation in the aging group and translocated to the outer membrane of mitochondria, co-regulating DRP1; thereby increasing mitochondrial fission. A significant reduction in the quality of mitochondria in the aging group, a serious imbalance, and a significant reduction in energy, causing metabolism shift toward glycolysis, were also reported. Since PGAM5 is eliminated, the mitochondrial function and metabolism of aging cells are partially reversed. A total of 70 patients undergoing in vitro fertilization (IVF) treatment were recruited in this clinical study. The high expression of PGAM5 in the cumulus cells is negatively correlated with the pregnancy rate of infertile patients. Hence, PGAM5 has immense potential to be used as a diagnostic marker.
| S-EPMC8844125 | biostudies-literature