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Nature Reviews. Molecular Cell Biology Aug 2023The microtubule-based spindle orchestrates chromosome segregation during cell division. Following more than a century of study, many components and pathways contributing... (Review)
Review
The microtubule-based spindle orchestrates chromosome segregation during cell division. Following more than a century of study, many components and pathways contributing to spindle assembly have been described, but how the spindle robustly assembles remains incompletely understood. This process involves the self-organization of a large number of molecular parts - up to hundreds of thousands in vertebrate cells - whose local interactions give rise to a cellular-scale structure with emergent architecture, mechanics and function. In this Review, we discuss key concepts in our understanding of spindle assembly, focusing on recent advances and the new approaches that enabled them. We describe the pathways that generate the microtubule framework of the spindle by driving microtubule nucleation in a spatially controlled fashion and present recent insights regarding the organization of individual microtubules into structural modules. Finally, we discuss the emergent properties of the spindle that enable robust chromosome segregation.
Topics: Spindle Apparatus; Microtubules; Cell Division; Chromosome Segregation
PubMed: 36977834
DOI: 10.1038/s41580-023-00584-0 -
Molecular Cell Oct 2020Cell division requires the assembly and organization of a microtubule spindle for the proper separation of chromosomes in mitosis and meiosis. Phase separation is an... (Review)
Review
Cell division requires the assembly and organization of a microtubule spindle for the proper separation of chromosomes in mitosis and meiosis. Phase separation is an emerging paradigm for understanding spatial and temporal regulation of a variety of cellular processes, including cell division. Phase-separated condensates have been recently discovered at many structures during cell division as a possible mechanism for properly localizing, organizing, and activating proteins involved in cell division. Here, we review how these condensates play roles in regulating microtubule density and organization and spindle assembly and function and in activating some of the key players in cell division. We conclude with perspectives on areas of future research for this exciting and rapidly advancing field.
Topics: Animals; Cell Division; Chromosomes; Humans; Meiosis; Microtubules; Spindle Apparatus
PubMed: 32860741
DOI: 10.1016/j.molcel.2020.08.007 -
Seminars in Cell & Developmental Biology Jul 2022Cytokinesis is a mechanism that separates dividing cells via constriction of a supramolecular structure, the contractile ring. In animal cells, three modes of... (Review)
Review
Cytokinesis is a mechanism that separates dividing cells via constriction of a supramolecular structure, the contractile ring. In animal cells, three modes of symmetry-breaking of cytokinesis result in unilateral cytokinesis, asymmetric cell division, and oriented cell division. Each mode of cytokinesis plays a significant role in tissue patterning and morphogenesis by the mechanisms that control the orientation and position of the contractile ring relative to the body axis. Despite its significance, the mechanisms involved in the symmetry-breaking of cytokinesis remain unclear in many cell types. Classical embryologists have identified that the geometric relationship between the mitotic spindle and cell cortex induces cytokinesis asymmetry; however, emerging evidence suggests that a concerted flow of compressional cell-cortex materials (cortical flow) is a spindle-independent driving force in spatial cytokinesis control. This review provides an overview of both classical and emerging mechanisms of cytokinesis asymmetry and their roles in animal development.
Topics: Actin Cytoskeleton; Animals; Cell Division; Cytokinesis; Spindle Apparatus
PubMed: 34955355
DOI: 10.1016/j.semcdb.2021.12.008 -
Cells Dec 2022The plasma membrane of eukaryotic cells is composed of a large number of lipid species that are laterally segregated into functional domains as well as asymmetrically... (Review)
Review
The plasma membrane of eukaryotic cells is composed of a large number of lipid species that are laterally segregated into functional domains as well as asymmetrically distributed between the outer and inner leaflets. Additionally, the spatial distribution and organization of these lipids dramatically change in response to various cellular states, such as cell division, differentiation, and apoptosis. Division of one cell into two daughter cells is one of the most fundamental requirements for the sustenance of growth in all living organisms. The successful completion of cytokinesis, the final stage of cell division, is critically dependent on the spatial distribution and organization of specific lipids. In this review, we discuss the properties of various lipid species associated with cytokinesis and the mechanisms involved in their polarization, including forward trafficking, endocytic recycling, local synthesis, and cortical flow models. The differences in lipid species requirements and distribution in mitotic vs. male meiotic cells will be discussed. We will concentrate on sphingolipids and phosphatidylinositols because their transbilayer organization and movement may be linked via the cytoskeleton and thus critically regulate various steps of cytokinesis.
Topics: Male; Humans; Cytokinesis; Cell Division; Cell Membrane; Biological Transport; Phosphatidylinositols
PubMed: 36552741
DOI: 10.3390/cells11243977 -
The Journal of Biological Chemistry Nov 2023Cell cycle errors can lead to mutations, chromosomal instability, or death; thus, the precise control of cell cycle progression is essential for viability. The... (Review)
Review
Cell cycle errors can lead to mutations, chromosomal instability, or death; thus, the precise control of cell cycle progression is essential for viability. The nutrient-sensing posttranslational modification, O-GlcNAc, regulates the cell cycle allowing one central control point directing progression of the cell cycle. O-GlcNAc is a single N-acetylglucosamine sugar modification to intracellular proteins that is dynamically added and removed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. These enzymes act as a rheostat to fine-tune protein function in response to a plethora of stimuli from nutrients to hormones. O-GlcNAc modulates mitogenic growth signaling, senses nutrient flux through the hexosamine biosynthetic pathway, and coordinates with other nutrient-sensing enzymes to progress cells through Gap phase 1 (G). At the G/S transition, O-GlcNAc modulates checkpoint control, while in S Phase, O-GlcNAcylation coordinates the replication fork. DNA replication errors activate O-GlcNAcylation to control the function of the tumor-suppressor p53 at Gap Phase 2 (G). Finally, in mitosis (M phase), O-GlcNAc controls M phase progression and the organization of the mitotic spindle and midbody. Critical for M phase control is the interplay between OGT and OGA with mitotic kinases. Importantly, disruptions in OGT and OGA activity induce M phase defects and aneuploidy. These data point to an essential role for the O-GlcNAc rheostat in regulating cell division. In this review, we highlight O-GlcNAc nutrient sensing regulating G, O-GlcNAc control of DNA replication and repair, and finally, O-GlcNAc organization of mitotic progression and spindle dynamics.
Topics: Acetylglucosamine; Acetylglucosaminidase; Mitosis; Mutation; N-Acetylglucosaminyltransferases; Protein Processing, Post-Translational; Signal Transduction; Humans; Animals
PubMed: 37820866
DOI: 10.1016/j.jbc.2023.105330 -
Nucleus (Austin, Tex.) Dec 2022The kinetochore is a large proteinaceous structure assembled on the centromeres of chromosomes. The complex machinery links chromosomes to the mitotic spindle and is... (Review)
Review
The kinetochore is a large proteinaceous structure assembled on the centromeres of chromosomes. The complex machinery links chromosomes to the mitotic spindle and is essential for accurate chromosome segregation during cell division. The kinetochore is composed of two submodules: the inner and outer kinetochore. The inner kinetochore is assembled on centromeric chromatin and persists with centromeres throughout the cell cycle. The outer kinetochore attaches microtubules to the inner kinetochore, and assembles only during mitosis. The review focuses on recent advances in our understanding of the mechanisms governing the proper assembly of the outer kinetochore during mitosis and highlights open questions for future investigation.
Topics: Cell Cycle Checkpoints; Centromere; Chromosome Segregation; Kinetochores; Mitosis; Spindle Apparatus
PubMed: 36037227
DOI: 10.1080/19491034.2022.2115246 -
Proceedings. Biological Sciences Mar 2022Ageing, death, and potential immortality lie at the heart of biology, but two seemingly incompatible paradigms coexist in different research communities and have done... (Review)
Review
Ageing, death, and potential immortality lie at the heart of biology, but two seemingly incompatible paradigms coexist in different research communities and have done since the nineteenth century. The universal senescence paradigm sees senescence as inevitable in all cells. Damage accumulates. The potential immortality paradigm sees some cells as potentially immortal, especially unicellular organisms, germ cells and cancerous cells. Recent research with animal cells, yeasts and bacteria show that damaged cell constituents do in fact build up, but can be diluted by growth and cell division, especially by asymmetric cell division. By contrast, mammalian embryonic stem cells and many cancerous and 'immortalized' cell lines divide symmetrically, and yet replicate indefinitely. How do they acquire their potential immortality? I suggest they are rejuvenated by excreting damaged cell constituents in extracellular vesicles. If so, our understanding of cellular senescence, rejuvenation and potential immortality could be brought together in a new synthesis, which I call the cellular rejuvenation hypothesis: damaged cell constituents build up in all cells, but cells can be rejuvenated either by growth and cell division or, in 'immortal' cell lines, by excreting damaged cell constituents. In electronic supplementary material, appendix, I outline nine ways in which this hypothesis could be tested.
Topics: Aging; Animals; Cell Division; Cellular Senescence; Mammals; Rejuvenation
PubMed: 35232226
DOI: 10.1098/rspb.2021.2434 -
Nature Chemical Biology Aug 2021Extracellular peptidoglycan-linked polysaccharide modifications mediate cell morphology, division, and autolysis in some Gram-positive bacterial pathogens. A new study...
Extracellular peptidoglycan-linked polysaccharide modifications mediate cell morphology, division, and autolysis in some Gram-positive bacterial pathogens. A new study shows that the degree and location of a specific modification controls peptidoglycan hydrolysis and placement of the axis of cell division.
Topics: Cell Division; Cues; Spindle Apparatus
PubMed: 34045746
DOI: 10.1038/s41589-021-00818-2 -
Journal of Cell Science Apr 2020Bacterial cell division is initiated by the midcell assembly of polymers of the tubulin-like GTPase FtsZ. The FtsZ ring (Z-ring) is a discontinuous structure made of... (Review)
Review
Bacterial cell division is initiated by the midcell assembly of polymers of the tubulin-like GTPase FtsZ. The FtsZ ring (Z-ring) is a discontinuous structure made of dynamic patches of FtsZ that undergo treadmilling motion. Roughly a dozen additional essential proteins are recruited to the division site by the dynamic Z-ring scaffold and subsequently activate cell wall synthesis to drive cell envelope constriction during division. In this Cell Science at a Glance article and the accompanying poster, we summarize our understanding of the assembly and activation of the bacterial cell division machinery. We introduce polymerization properties of FtsZ and discuss our current knowledge of divisome assembly and activation. We further highlight the intimate relationship between the structure and dynamics of FtsZ and the movement and activity of cell wall synthases at the division site, before concluding with a perspective on the most important open questions on bacterial cell division.
Topics: Bacterial Proteins; Cell Division; Cell Wall; Cytokinesis; Cytoskeletal Proteins
PubMed: 32269092
DOI: 10.1242/jcs.237057 -
Nature Chemical Biology Jun 2021Components of the cell division machinery typically function at varying cell cycle stages and intracellular locations. To dissect cellular mechanisms during the rapid... (Review)
Review
Components of the cell division machinery typically function at varying cell cycle stages and intracellular locations. To dissect cellular mechanisms during the rapid division process, small-molecule probes act as complementary approaches to genetic manipulations, with advantages of temporal and in some cases spatial control and applicability to multiple model systems. This Review focuses on recent advances in chemical probes and applications to address select questions in cell division. We discuss uses of both enzyme inhibitors and chemical inducers of dimerization, as well as emerging techniques to promote future investigations. Overall, these concepts may open new research directions for applying chemical probes to advance cell biology.
Topics: Animals; Cell Biology; Cell Cycle; Cell Division; Genetic Techniques; Humans
PubMed: 34035515
DOI: 10.1038/s41589-021-00798-3