Mechanism Of Cell Division Research Articles

Tracing back variations in archaeal ESCRT-based cell division to protein domain architectures.

The Endosomal Sorting Complex Required for Transport (ESCRT) system is a multi-protein machinery that is involved in cell division of both Eukaryotes and Archaea. This spread across domains of life suggests that a precursor ESCRT machinery existed already at an evolutionary early stage of life, making it a promising candidate for the (re)construction of a minimal cell division machinery. There are, however, only few experimental data about ESCRT machineries in Archaea, due to high technical challenges in cultivation and microscopy. Here, we analyse the proteins of ESCRT machineries in archaea bioinformatically on a protein domain level, to enable mechanistical comparison without such challenging experiments. First, we infer that there are at least three different cell division mechanisms utilizing ESCRT proteins in archaea, probably similar in their constriction mechanisms but different in membrane tethering. Second, we show that ESCRT proteins in the archaeal super-phylum Asgard are highly similar to eukaryotic ESCRT proteins, strengthening the recently developed idea that all Eukaryotes descended from archaea. Third, we reconstruct a plausible evolutionary development of ESCRT machineries and suggest that a simple ESCRT-based constriction machinery existed in the last archaeal common ancestor. These findings not only give very interesting insights into the likely evolution of cell division in Archaea and Eukaryotes, but also offer new research avenues by suggesting hypothesis-driven experiments for both, cell biology and bottom-up synthetic biology.

The correlation between cell and nucleus size is explained by an eukaryotic cell growth model.

In eukaryotes, the cell volume is observed to be strongly correlated with the nuclear volume. The slope of this correlation depends on the cell type, growth condition, and the physical environment of the cell. We develop a computational model of cell growth and proteome increase, incorporating the kinetics of amino acid import, protein/ribosome synthesis and degradation, and active transport of proteins between the cytoplasm and the nucleoplasm. We also include a simple model of ribosome biogenesis and assembly. Results show that the cell volume is tightly correlated with the nuclear volume, and the cytoplasm-nucleoplasm transport rates strongly influence the cell growth rate as well as the cell/nucleus volume ratio (C/N ratio). Ribosome assembly and the ratio of ribosomal proteins to mature ribosomes also influence the cell volume and the cell growth rate. We find that in order to regulate the cell growth rate and the cell/nucleus volume ratio, the cell must optimally control groups of kinetic and transport parameters together, which could explain the quantitative roles of canonical growth pathways. Finally, although not explicitly demonstrated in this work, we point out that it is possible to construct a detailed proteome distribution using our model and RNAseq data, provided that a quantitative cell division mechanism is known.

Cell Cycle Regulation by Heat Shock Transcription Factors.

Cell division and cell cycle mechanism has been studied for 70 years. This research has revealed that the cell cycle is regulated by many factors, including cyclins and cyclin-dependent kinases (CDKs). Heat shock transcription factors (HSFs) have been noted as critical proteins for cell survival against various stresses; however, recent studies suggest that HSFs also have important roles in cell cycle regulation-independent cell-protective functions. During cell cycle progression, HSF1, and HSF2 bind to condensed chromatin to provide immediate precise gene expression after cell division. This review focuses on the function of these HSFs in cell cycle progression, cell cycle arrest, gene bookmarking, mitosis and meiosis.

Role of histone deacetylase inhibitors in androgenic callus induction of Oryza sativa sub indica, in sight into evolution and mode of action of histone deacetylase genes.

The potential of paddy breeding has reached its pinnacle, and hybrids have been the principal research outcome. Hence, our hypothesis was based on improvising the callus induction efficiency of recalcitrant Oryza sativa sub. indica hybrids by intervening into their cellular functions like cell division and histone regulation for the production of doubled haploids, a better output compared to hybrids. Insight into the mechanism of cell division is the foremost concern in altering the same and hence studies on evolution, expression and action of histone deacetylase and its 12 genes (9 HDA and 3 HD-tunin genes) were chosen in the hypothesis. Expression of HDA genes at three stages (anther dehiscence, 1st callusing and second callusing stages) with inhibitor (trichostatin-A) interventions indicated 1st callusing stage as the most important in influencing callus induction and also the genes HDA19, 6, 15 and 5 were the most important. TSA alone had a significant impact on the regulation of the genes HDT 702, HDA19, HDA9, and HDA6. Higher expression of HDA19 and HDA6 was involved in maximizing callus induction; HDA15 had an antagonistic expression compared to HDA19/6 and might be involved in chlorophyll regulation during regeneration. Results of evolutionary analysis on histone deacetylases indicated a long and single lineage of origin denoting its importance in the basic cellular functions. The tubulin deacetylation gene HDA5, which was exclusively found in dicotyledons, had a recent evolutionary history only from terrestrial plants, and also had significant conservation in its motifs and NLS region. By combating the recalcitrant nature of Indica cultivars, molecular editing on a combination of HDA genes will enhance the callus induction and regeneration efficiency of the next generation of doubled haploids, therby improving the total yield.

Methods for Investigating Cell Division Mechanisms in C. elegans.

The nematode Caenorhabditis elegans is a widely used model organism for the study of mitotic and meiotic cell division. These self-fertilizing worms are particularly advantageous for such studies because they rapidly reproduce (each worm lays ~250 eggs in only 3-4days) and the cell division machinery is highly conserved between worms and humans. Worms are also genetically tractable and proteins can be readily depleted using RNA interference (RNAi), allowing for the characterization of protein function in vivo. To assess phenotypes, spindles can be directly visualized within the worm using fluorescent protein tags or embryos can be dissected out of the worm and immunostained. A combination of these techniques allows comprehensive characterization of a protein's function in a relatively short time span. Here, we describe methods for each of these techniques: RNA interference through feeding, in utero live imaging, in utero fixed imaging, and immunofluorescence.

The Pneumococcal Divisome: Dynamic Control of Streptococcus pneumoniae Cell Division.

Cell division in Streptococcus pneumoniae (pneumococcus) is performed and regulated by a protein complex consisting of at least 14 different protein elements; known as the divisome. Recent findings have advanced our understanding of the molecular events surrounding this process and have provided new understanding of the mechanisms that occur during the division of pneumococcus. This review will provide an overview of the key protein complexes and how they are involved in cell division. We will discuss the interaction of proteins in the divisome complex that underpin the control mechanisms for cell division and cell wall synthesis and remodelling that are required in S. pneumoniae, including the involvement of virulence factors and capsular polysaccharides.

CdrS Is a Global Transcriptional Regulator Influencing Cell Division in Haloferax volcanii.

ABSTRACTTranscriptional regulators that integrate cellular and environmental signals to control cell division are well known in bacteria and eukaryotes, but their existence is poorly understood in archaea. We identified a conserved gene (cdrS) that encodes a small protein and is highly transcribed in the model archaeon Haloferax volcanii. The cdrS gene could not be deleted, but CRISPR interference (CRISPRi)-mediated repression of the cdrS gene caused slow growth and cell division defects and changed the expression of multiple genes and their products associated with cell division, protein degradation, and metabolism. Consistent with this complex regulatory network, overexpression of cdrS inhibited cell division, whereas overexpression of the operon encoding both CdrS and a tubulin-like cell division protein (FtsZ2) stimulated division. Chromatin immunoprecipitation-DNA sequencing (ChIP-Seq) identified 18 DNA-binding sites of the CdrS protein, including one upstream of the promoter for a cell division gene, ftsZ1, and another upstream of the essential gene dacZ, encoding diadenylate cyclase involved in c-di-AMP signaling, which is implicated in the regulation of cell division. These findings suggest that CdrS is a transcription factor that plays a central role in a regulatory network coordinating metabolism and cell division.

SepF is the FtsZ anchor in archaea, with features of an ancestral cell division system

Most archaea divide by binary fission using an FtsZ-based system similar to that of bacteria, but they lack many of the divisome components described in model bacterial organisms. Notably, among the multiple factors that tether FtsZ to the membrane during bacterial cell constriction, archaea only possess SepF-like homologs. Here, we combine structural, cellular, and evolutionary analyses to demonstrate that SepF is the FtsZ anchor in the human-associated archaeon Methanobrevibacter smithii. 3D super-resolution microscopy and quantitative analysis of immunolabeled cells show that SepF transiently co-localizes with FtsZ at the septum and possibly primes the future division plane. M. smithii SepF binds to membranes and to FtsZ, inducing filament bundling. High-resolution crystal structures of archaeal SepF alone and in complex with the FtsZ C-terminal domain (FtsZCTD) reveal that SepF forms a dimer with a homodimerization interface driving a binding mode that is different from that previously reported in bacteria. Phylogenetic analyses of SepF and FtsZ from bacteria and archaea indicate that the two proteins may date back to the Last Universal Common Ancestor (LUCA), and we speculate that the archaeal mode of SepF/FtsZ interaction might reflect an ancestral feature. Our results provide insights into the mechanisms of archaeal cell division and pave the way for a better understanding of the processes underlying the divide between the two prokaryotic domains.

Lewis Wolpert (1929–2021)

Lewis Wolpert (1929–2021)

Streptococcus suis MsmK: Novel Cell Division Protein Interacting with FtsZ and Maintaining Cell Shape.

ABSTRACTBacteria of different shapes have adopted distinct mechanisms to faithfully coordinate morphogenesis and segregate their chromosomes prior to cell division. Despite recent focuses and advances, the mechanism of cell division in ovococci remains largely unknown. Streptococcus suis, a major zoonotic pathogen that causes problems in human health and in the global swine industry, is an elongated and ellipsoid bacterium that undergoes successive parallel splitting perpendicular to its long axis. Studies on cell cycle processes in this bacterium are limited. Here, we report that MsmK (multiple sugar metabolism protein K), an ATPase that contributes to the transport of multiple carbohydrates, has a novel role as a cell division protein in S. suis. MsmK can display ATPase and GTPase activities, interact with FtsZ via the N terminus of MsmK, and promote the bundling of FtsZ protofilaments in a GTP-dependent manner in vitro. Deletion of the C-terminal region or the Walker A or B motif affects the affinity between MsmK and FtsZ and decreases the ability of MsmK to promote FtsZ protofilament bundling. MsmK can form a complex with FtsZ in vivo, and its absence is not lethal but results in long chains and short, occasionally anuclear daughter cells. Superresolution microscopy revealed that the lack of MsmK in cells leads to normal septal peptidoglycan walls in mother cells but disturbed cell elongation and peripheral peptidoglycan synthesis. In summary, MsmK is a novel cell division protein that maintains cell shape and is involved in the synthesis of the peripheral cell wall.IMPORTANCE Bacterial cell division is a highly ordered process regulated in time and space and is a potential target for the development of antimicrobial drugs. Bacteria of distinct shapes depend on different cell division mechanisms, but the mechanisms used by ovococci remain largely unknown. Here, we focused on the zoonotic pathogen Streptococcus suis and identified a novel cell division protein named MsmK, which acts as an ATPase of the ATP-binding cassette-type carbohydrate transport system. MsmK has GTPase and ATPase activities. In vitro protein assays showed that MsmK interacts with FtsZ and promotes FtsZ protofilament bundling that relies on GTP. Superresolution microscopy revealed that MsmK maintains cell shape and is involved in peripheral peptidoglycan synthesis. Knowledge of the multiple functions of MsmK may broaden our understanding of known cell division processes. Further studies in this area will elucidate how bacteria can faithfully and continually multiply in a constantly changing environment.

Plant stem cell research is uncovering the secrets of longevity and persistent growth.

SummaryPlant stem cells have several extraordinary features: they are generated de novo during development and regeneration, maintain their pluripotency, and produce another stem cell niche in an orderly manner. This enables plants to survive for an extended period and to continuously make new organs, representing a clear difference in their developmental program from animals. To uncover regulatory principles governing plant stem cell characteristics, our research project ‘Principles of pluripotent stem cells underlying plant vitality’ was launched in 2017, supported by a Grant‐in‐Aid for Scientific Research on Innovative Areas from the Japanese government. Through a collaboration involving 28 research groups, we aim to identify key factors that trigger epigenetic reprogramming and global changes in gene networks, and thereby contribute to stem cell generation. Pluripotent stem cells in the shoot apical meristem are controlled by cytokinin and auxin, which also play a crucial role in terminating stem cell activity in the floral meristem; therefore, we are focusing on biosynthesis, metabolism, transport, perception, and signaling of these hormones. Besides, we are uncovering the mechanisms of asymmetric cell division and of stem cell death and replenishment under DNA stress, which will illuminate plant‐specific features in preserving stemness. Our technology support groups expand single‐cell omics to describe stem cell behavior in a spatiotemporal context, and provide correlative light and electron microscopic technology to enable live imaging of cell and subcellular dynamics at high spatiotemporal resolution. In this perspective, we discuss future directions of our ongoing projects and related research fields.

Monodirectional Evolutional Symport Tissue P Systems With Promoters and Cell Division

Monodirectional tissue P systems with promoters are natural inspired parallel computing paradigms, where only symport rules are permitted, and with the restriction of “monodirectionality”, objects for two given regions are transferred in one direction. In this article, a novel kind of P systems, monodirectional evolutional symport tissue P systems with promoters (MESTP P systems) is raised, where objects may be revised during the movement between two regions. The computational theory of MESTP P systems that rules are employed in a flat maximally parallel pattern is investigated. We prove that finite natural number sets are created by MESTP P systems applying one cell, at most 1 promoter and all evolutional symport rules having a maximal length 2 or with arbitrary number of cells, promoters and all evolutional symport rules having a maximal length 2. MESTP P systems are Turing universal when two cells, at most 1 promoter and all evolutional symport rules having a maximal length 2 are employed. In addition, with the help of cell division mechanism, monodirectional evolutional symport tissue P systems with promoters and cell division (MESTPD P systems) are employed to solve NP-complete (the SAT) problem, where system uses at most 1 promoter and all evolutional symport rules having a maximal length 3. These results show that MESTP(D) P systems are still computationally powerful even if monodirectionality control mechanism is imposed, thereby developing membrane algorithms for MESTP(D) P systems is theoretically possible as well as potentially exploitable.

Molecular mechanism of cytokinin-activated cell division in Arabidopsis.

Mitogens trigger cell division in animals. In plants, cytokinins, a group of phytohormones derived from adenine, stimulate cell proliferation. Cytokinin signaling is initiated by membrane-associated histidine kinase receptors and transduced through a phosphorelay system. We show that in the Arabidopsis shoot apical meristem (SAM), cytokinin regulates cell division by promoting nuclear shuttling of Myb-domain protein 3R4 (MYB3R4), a transcription factor that activates mitotic gene expression. Newly synthesized MYB3R4 protein resides predominantly in the cytoplasm. At the G2-to-M transition, rapid nuclear accumulation of MYB3R4-consistent with an associated transient peak in cytokinin concentration-feeds a positive feedback loop involving importins and initiates a transcriptional cascade that drives mitosis and cytokinesis. An engineered nuclear-restricted MYB3R4 mimics the cytokinin effects of enhanced cell proliferation and meristem growth.

The Investigation of Antimutagenic Effects on Chromosomes and Cell Division Mechanisms against Mitomycine C in Human Lymphocyte Culture of Liquid Extracts Obtained from Blueberry (Vaccinium myrtillus L.) and Raspberry (Rubus idaeus L.)

Aims: In this study, we determined that whether the liquid extracts of the above-ground parts of Vaccinium myrtillus L. and Rubus idaeus L. have antimutagenic effects against mitomycin C in human peripheral lymphocytes, chromosome aberration (CA), micronucleus (MN) and mitotic index (MI) tests.
 Methodology: Blood samples of the negative control group (Group I) were allowed to react in a cell culture medium without any treatment, while positive control group (Group II) was allowed to interact in a cell culture medium supplemented with mitomycin-C (MMC) at a dose of 0.3 μL /mL for each chromosome medium. Blood samples of the other groups were allowed to react for 24 hours with 0.3 μL /mL MMC and V. myrtillus L. (Group III, IV, V and VI), and R. idaeus L. (VII, VIII, IX and X) extracts in 0.2 μL /mL, 0.4 μL /mL, 0.8 μL /mL and 1.6 μL /mL doses for each of cell cultures. At the end of the incubation period, culture cells were evaluated by chromosomal aberrations, mitotic, micronucleus and nuclear division index tests.
 Results: Compared with Group II, it was determined that mitotic, nuclear division and nuclear cytotoxic cleavage indices were increased when chromosome aberrations and micronucleus indexes were decreased in extract groups. When we compared to extract groups and group II, we observed that chromosome aberrations and micronucleus index decreased in extract groups, while mitotic, nuclear division and nuclear cytotoxic cleavage indices were increased.
 Conclusion: It was concluded that aqueous extracts of V. myrtillus L. and Rubus idaeus L. had significantly antimutagenic effects on the human peripheral lymphocyte cells at the working doses.

Evidences of Different Drought Sensitivity in Xylem Cell Developmental Processes in South Siberia Scots Pines

Research Highlights: This study emphasized the importance of multi-parameter analyses along ecological gradients for a more holistic understanding of the complex mechanism of tree-ring formation. Background and Objectives: The analysis of climatic signals from cell anatomical features measured along series of tree-rings provides mechanistic details on how environmental drivers rule tree-ring formation. However, the processes of cell development might not be independent, limiting the interpretation of the cell-based climatic signal. In this study, we investigated the variability, intercorrelations and climatic drivers of wood anatomical parameters, resulting from consequent cell developmental processes. Materials and Methods: The study was performed on thin cross-sections from wood cores sampled at ~1.3 m stem height from mature trees of Pinus sylvestris L. growing at five sampling sites along an ecological gradient from cold and wet to hot and dry within continental Southern Siberia. Tracheid number per radial file, their diameters and wall thicknesses were measured along the radial direction from microphotographs for five trees per site. These parameters were then averaged at each site for earlywood and latewood over the last 50 tree rings to build site chronologies. Their correlations among themselves and with 21-day moving climatic series were calculated. Results: Our findings showed that wood formation was not simply the result of environmentally driven independent subprocesses of cell division, enlargement and wall deposition. These processes appear to be interconnected within each zone of the ring, as well as between earlywood and latewood. However, earlywood parameters tend to have more distinctive climatic responses and lower intercorrelations. On the other hand, there are clear indications that the mechanisms of cell division and enlargement share similar climatic drivers and are more sensitive to water limitation than the process of wall deposition. Conclusions: Indications were provided that (i) earlywood formation left a legacy on latewood formation, (ii) cell division and enlargement shared more similar drivers between each other than with wall deposition, and (iii) the mechanism of cell division and enlargement along the gradient switch from water to heat limitations at different thresholds than wall deposition.

Design optimization of metamaterial units using a genetic algorithm based optimization methodology

Purpose The purpose of this paper is to develop a pertinent design optimization methodology for symmetric designs of a metamaterial (MM) unit. Design/methodology/approach A cell division mechanism is introduced and used to design a new selecting mechanism in the proposed algorithm, a non-dominated sorting cellular genetic algorithm (NSCGA). Findings The numerical results on solving standard multi-objective test functions and a prototype MM unit positively demonstrate the advantages of the proposed NSCGA. Originality/value A new NSGAII-based optimization algorithm, NSCGA, for multi-objective optimization designs of a MM unit is proposed.

The proteasome controls ESCRT-III-mediated cell division in an archaeon.

Sulfolobus acidocaldarius is the closest experimentally tractable archaeal relative of eukaryotes and, despite lacking obvious cyclin-dependent kinase and cyclin homologs, has an ordered eukaryote-like cell cycle with distinct phases of DNA replication and division. Here, in exploring the mechanism of cell division in S. acidocaldarius, we identify a role for the archaeal proteasome in regulating the transition from the end of one cell cycle to the beginning of the next. Further, we identify the archaeal ESCRT-III homolog, CdvB, as a key target of the proteasome and show that its degradation triggers division by allowing constriction of the CdvB1:CdvB2 ESCRT-III division ring. These findings offer a minimal mechanism for ESCRT-III-mediated membrane remodeling and point to a conserved role for the proteasome in eukaryotic and archaeal cell cycle control.

A Supersymmetry and Quantum Cryptosystem with Path Integral Approach in Biology

The source of cancerous mutations and the relationship to telomeres is explained in an alternative way. We define the smallest subunit in the genetic code as a loop braid group element. The loop braid group is suitable to be defined as a configuration space in the process of converting the information written in the DNA into the structure of a folded protein. This smallest subunit, or a flying ring in our definition, is a representation of 8-spinor field in the supermanifold of the genetic code. The image of spectral analysis from the tensor correlation of mutation genes as our biological system is produced. We apply the loop braid group for biology and authentication in quantum cryptography to understand the cell cocycle and division mechanism of telomerase aging. A quantum biological cryptosystem is used to detect cancer signatures in 36 genotypes of the bone ALX1 cancer gene. The loop braid group with the RSA algorithm is applied for the calculation of public and private keys as cancer signatures in genes. The key role of this approach is the use of the Chern–Simons current and then the fiber bundle representation of the genetic code that allows a quantization procedure.

Perturbation biology links temporal protein changes to drug responses in a melanoma cell line.

Cancer cells have genetic alterations that often directly affect intracellular protein signaling processes allowing them to bypass control mechanisms for cell death, growth and division. Cancer drugs targeting these alterations often work initially, but resistance is common. Combinations of targeted drugs may overcome or prevent resistance, but their selection requires context-specific knowledge of signaling pathways including complex interactions such as feedback loops and crosstalk. To infer quantitative pathway models, we collected a rich dataset on a melanoma cell line: Following perturbation with 54 drug combinations, we measured 124 (phospho-)protein levels and phenotypic response (cell growth, apoptosis) in a time series from 10 minutes to 67 hours. From these data, we trained time-resolved mathematical models that capture molecular interactions and the coupling of molecular levels to cellular phenotype, which in turn reveal the main direct or indirect molecular responses to each drug. Systematic model simulations identified novel combinations of drugs predicted to reduce the survival of melanoma cells, with partial experimental verification. This particular application of perturbation biology demonstrates the potential impact of combining time-resolved data with modeling for the discovery of new combinations of cancer drugs.

Principles and mechanisms of asymmetric cell division.

Asymmetric cell division (ACD) is an evolutionarily conserved mechanism used by prokaryotes and eukaryotes alike to control cell fate and generate cell diversity. A detailed mechanistic understanding of ACD is therefore necessary to understand cell fate decisions in health and disease. ACD can be manifested in the biased segregation of macromolecules, the differential partitioning of cell organelles, or differences in sibling cell size or shape. These events are usually preceded by and influenced by symmetry breaking events and cell polarization. In this Review, we focus predominantly on cell intrinsic mechanisms and their contribution to cell polarization, ACD and binary cell fate decisions. We discuss examples of polarized systems and detail how polarization is established and, whenever possible, how it contributes to ACD. Established and emerging model organisms will be considered alike, illuminating both well-documented and underexplored forms of polarization and ACD.