scholarly journals HIPK2 Phosphorylates the Microtubule-Severing Enzyme Spastin at S268 for Abscission

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 684 ◽  
Author(s):  
Pisciottani ◽  
Biancolillo ◽  
Ferrara ◽  
Valente ◽  
Sardina ◽  
...  
Keyword(s):  
Cell Division ◽  
Physical Separation ◽  
Microtubule Severing ◽  
Daughter Cells ◽  
Cellular Pathways ◽  
Novel Target

Abscission is the final step of cell division, mediating the physical separation of the two daughter cells. A key player in this process is the microtubule-severing enzyme spastin that localizes at the midbody where its activity is crucial to cut microtubules and culminate the cytokinesis. Recently, we demonstrated that HIPK2, a multifunctional kinase involved in several cellular pathways, contributes to abscission and prevents tetraploidization. Here, we show that HIPK2 binds and phosphorylates spastin at serine 268. During cytokinesis, the midbody-localized spastin is phosphorylated at S268 in HIPK2-proficient cells. In contrast, no spastin is detectable at the midbody in HIPK2-depleted cells. The non-phosphorylatable spastin-S268A mutant does not localize at the midbody and cannot rescue HIPK2-depleted cells from abscission defects. In contrast, the phosphomimetic spastin-S268D mutant localizes at the midbody and restores successful abscission in the HIPK2-depleted cells. These results show that spastin is a novel target of HIPK2 and that HIPK2-mediated phosphorylation of spastin contributes to its midbody localization for successful abscission.

scholarly journals Extrachromosomal Histone H2B Contributes to the Formation of the Abscission Site for Cell Division

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1391 ◽  
Author(s):  
Laura Monteonofrio ◽  
Davide Valente ◽  
Cinzia Rinaldo ◽  
Silvia Soddu
Keyword(s):  
Cell Division ◽  
Chromatin Structure ◽  
Late Stage ◽  
Intercellular Bridge ◽  
Histone H2b ◽  
Physical Separation ◽  
Daughter Cells ◽  
Dna And Rna ◽  
Constitutive Components

Histones are constitutive components of nucleosomes and key regulators of chromatin structure. We previously observed that an extrachromosomal histone H2B (ecH2B) localizes at the intercellular bridge (ICB) connecting the two daughter cells during cytokinesis independently of DNA and RNA. Here, we show that ecH2B binds and colocalizes with CHMP4B, a key component of the ESCRT-III machinery responsible for abscission, the final step of cell division. Abscission requires the formation of an abscission site at the ICB where the ESCRT-III complex organizes into narrowing cortical helices that drive the physical separation of sibling cells. ecH2B depletion does not prevent membrane cleavage rather results in abscission delay and accumulation of abnormally long and thin ICBs. In the absence of ecH2B, CHMP4B and other components of the fission machinery, such as IST1 and Spastin, are recruited to the ICB and localize at the midbody. However, in the late stage of abscission, these fission factors fail to re-localize at the periphery of the midbody and the abscission site fails to form. These results show that extrachromosomal activity of histone H2B is required in the formation of the abscission site and the proper localization of the fission machinery.

scholarly journals The postmitotic midbody: Regulating polarity, stemness, and proliferation

2019 ◽  
Vol 218 (12) ◽  
pp. 3903-3911 ◽  
Author(s):  
Eric Peterman ◽  
Rytis Prekeris
Keyword(s):  
Cell Division ◽  
Cell Polarity ◽  
Final Stage ◽  
Cell Membranes ◽  
Daughter Cell ◽  
Endocytic Trafficking ◽  
Microtubule Severing ◽  
Daughter Cells ◽  
Cytoskeleton Dynamics

Abscission, the final stage of cell division, requires well-orchestrated changes in endocytic trafficking, microtubule severing, actin clearance, and the physical sealing of the daughter cell membranes. These processes are highly regulated, and any missteps in localized membrane and cytoskeleton dynamics often lead to a delay or a failure in cell division. The midbody, a microtubule-rich structure that forms during cytokinesis, is a key regulator of abscission and appears to function as a signaling platform coordinating cytoskeleton and endosomal dynamics during the terminal stages of cell division. It was long thought that immediately following abscission and the conclusion of cell division, the midbody is either released or rapidly degraded by one of the daughter cells. Recently, the midbody has gained prominence for exerting postmitotic functions. In this review, we detail the role of the midbody in orchestrating abscission, as well as discuss the relatively new field of postabscission midbody biology, particularly focusing on how it may act to regulate cell polarity and its potential to regulate cell tumorigenicity or stemness.

scholarly journals Making the Final Cut — Mechanisms Mediating the Abscission Step of Cytokinesis

2010 ◽  
Vol 10 ◽  
pp. 1424-1434 ◽  
Author(s):  
John A. Schiel ◽  
Rytis Prekeris
Keyword(s):  
Plasma Membrane ◽  
Cell Division ◽  
Cleavage Plane ◽  
Mitotic Cell ◽  
Dense Region ◽  
Contractile Ring ◽  
Physical Separation ◽  
Daughter Cells ◽  
Considerable Controversy ◽  
The Subject

Cytokinesis is the final stage of mitotic cell division that results in a physical separation of two daughter cells. Cytokinesis begins in the early stages of anaphase after the positioning of the cleavage plane and after the chromosomes segregate. This involves the recruitment and assembly of an actomyosin contractile ring, which constricts the plasma membrane and compacts midzone microtubules to form an electron-dense region, termed the midbody, located within an intracellular bridge. The resolution of this intracellular bridge, known as abscission, is the last step in cytokinesis that separates the two daughter cells. While much research has been done to delineate the mechanisms mediating actomyosin ring formation and contraction, the machinery that is responsible for abscission remains largely unclear. Recent work from several laboratories has demonstrated that dramatic changes occur in cytoskeleton and endosome dynamics, and are a prerequisite for abscission. However, the mechanistic details that regulate the final plasma membrane fusion during abscission are only beginning to emerge and are the subject of considerable controversy. Here we review recent studies within this field and discuss the proposed models of cell abscission.

Stimulated Virus Production in Vinblastine and Cytochalasin-Induced Multinucleate Cells

1970 ◽  
Vol 28 ◽  
pp. 186-187
Author(s):  
Krishan Awtar
Keyword(s):  
Cell Division ◽  
Normal Cell ◽  
Virus Production ◽  
Multinucleate Cells ◽  
Daughter Cells ◽  
Cell Divisions ◽  
Nuclear Membranes ◽  
Division 2 ◽  
Vinblastine Sulfate

Exposure of cells to low sublethal but mitosis-arresting doses of vinblastine sulfate (Velban) results in the initial arrest of cells in mitosis followed by their subsequent return to an “interphase“-like stage. A large number of these cells reform their nuclear membranes and form large multimicronucleated cells, some containing as many as 25 or more micronuclei (1). Formation of large multinucleate cells is also caused by cytochalasin, by causing the fusion of daughter cells at the end of an otherwise .normal cell division (2). By the repetition of this process through subsequent cell divisions, large cells with 6 or more nuclei are formed.

scholarly journals A complex containing the Sm protein CAR-1 and the RNA helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis elegans

2005 ◽  
Vol 171 (2) ◽  
pp. 267-279 ◽  
Author(s):  
Anjon Audhya ◽  
Francie Hyndman ◽  
Ian X. McLeod ◽  
Amy S. Maddox ◽  
John R. Yates ◽  
...  
Keyword(s):  
Cell Division ◽  
Caenorhabditis Elegans ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Rna Helicase ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Daughter Cells ◽  
Sm Protein ◽  
Spindle Structure

Cytokinesis completes cell division and partitions the contents of one cell to the two daughter cells. Here we characterize CAR-1, a predicted RNA binding protein that is implicated in cytokinesis. CAR-1 localizes to germline-specific RNA-containing particles and copurifies with the essential RNA helicase, CGH-1, in an RNA-dependent fashion. The atypical Sm domain of CAR-1, which directly binds RNA, is dispensable for CAR-1 localization, but is critical for its function. Inhibition of CAR-1 by RNA-mediated depletion or mutation results in a specific defect in embryonic cytokinesis. This cytokinesis failure likely results from an anaphase spindle defect in which interzonal microtubule bundles that recruit Aurora B kinase and the kinesin, ZEN-4, fail to form between the separating chromosomes. Depletion of CGH-1 results in sterility, but partially depleted worms produce embryos that exhibit the CAR-1–depletion phenotype. Cumulatively, our results suggest that CAR-1 functions with CGH-1 to regulate a specific set of maternally loaded RNAs that is required for anaphase spindle structure and cytokinesis.

scholarly journals Dem Anfang auf der Spur — die Suche nach DNA-Replikationsursprüngen

BIOspektrum ◽  
2021 ◽  
Vol 27 (3) ◽  
pp. 246-249
Author(s):  
Elisabeth Kruse ◽  
Stephan Hamperl
Keyword(s):  
Cell Division ◽  
Dna Synthesis ◽  
Genomic Dna ◽  
Genetic Material ◽  
Uniform Method ◽  
Replication Origins ◽  
Daughter Cells ◽  
Origins Of Replication ◽  
Mammalian Genomes ◽  
Comprehensive Manner

AbstractTimely and accurate duplication of DNA prior to cell division is a prerequisite for propagation of the genetic material to both daughter cells. DNA synthesis initiates at discrete sites, termed replication origins, and proceeds in a bidirectional manner until all genomic DNA is replicated. Despite the fundamental nature of these events, a uniform method that identifies origins of replication in a comprehensive manner is still missing. Here, we present currently available and discuss new approaches to map replication origins in mammalian genomes.

Effects of excess centromeres and excess telomeres on chromosome loss rates

1991 ◽  
Vol 11 (6) ◽  
pp. 2919-2928
Author(s):  
K W Runge ◽  
R J Wellinger ◽  
V A Zakian
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Division ◽  
Dna Sequences ◽  
Fluctuation Analysis ◽  
Chromosome Stability ◽  
Chromosome Loss ◽  
Division Iii ◽  
Daughter Cells ◽  
Chromosome Iii ◽  
Linear Chromosomes

The linear chromosomes of eukaryotes contain specialized structures to ensure their faithful replication and segregation to daughter cells. Two of these structures, centromeres and telomeres, are limited, respectively, to one and two copies per chromosome. It is possible that the proteins that interact with centromere and telomere DNA sequences are present in limiting amounts and could be competed away from the chromosomal copies of these elements by additional copies introduced on plasmids. We have introduced excess centromeres and telomeres into Saccharomyces cerevisiae and quantitated their effects on the rates of loss of chromosome III and chromosome VII by fluctuation analysis. We show that (i) 600 new telomeres have no effect on chromosome loss; (ii) an average of 25 extra centromere DNA sequences increase the rate of chromosome III loss from 0.4 x 10(-4) events per cell division to 1.3 x 10(-3) events per cell division; (iii) centromere DNA (CEN) sequences on circular vectors destabilize chromosomes more effectively than do CEN sequences on 15-kb linear vectors, and transcribed CEN sequences have no effect on chromosome stability. We discuss the different effects of extra centromere and telomere DNA sequences on chromosome stability in terms of how the cell recognizes these two chromosomal structures.

Cell division and morphogenesis of Limnaea eggs after treatment with heat pulses at successive stages in early division cycles

Development ◽  
1966 ◽  
Vol 16 (2) ◽  
pp. 321-337
Author(s):  
W. L. M. Geilenkirchen
Keyword(s):  
Cell Division ◽  
Produce Cell ◽  
Cleavage Cycle ◽  
Daughter Cells ◽  
Development And Differentiation ◽  
Heat Pulses

Cellular reproduction is related to a number of apparently independent processes of which the integrated results are bound to produce cell division. In eggs with determinate cleavage the results of division are daughter cells of a different prospective significance. It has been observed furthermore in Limnaea eggs that morphogenesis is related to periodically recurring cell activities in the first, second and third cleavage cycle (Geilenkirchen, 1964a, b). These activities of unknown nature are dissociable from the factors involved in cell division. Obviously in the course of one division cycle the egg discriminates between processes for the preparation of the next division and processes involved in morphogenesis and differentiation later on. The data published in this paper carry the notion that successive divisions represent well-defined steps of different significance for later development and differentiation.

scholarly journals Midbody: From the Regulator of Cytokinesis to Postmitotic Signaling Organelle

Medicina ◽  
2018 ◽  
Vol 54 (4) ◽  
pp. 53 ◽  
Author(s):  
Ieva Antanavičiūtė ◽  
Paulius Gibieža ◽  
Rytis Prekeris ◽  
Vytenis Skeberdis
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Intercellular Bridge ◽  
Large Protein ◽  
Daughter Cells ◽  
First Case ◽  
Tumorigenic Potential ◽  
The One ◽  
And Function ◽  
Protein Rich

Faithful cell division is crucial for successful proliferation, differentiation, and development of cells, tissue homeostasis, and preservation of genomic integrity. Cytokinesis is a terminal stage of cell division, leaving two genetically identical daughter cells connected by an intercellular bridge (ICB) containing the midbody (MB), a large protein-rich organelle, in the middle. Cell division may result in asymmetric or symmetric abscission of the ICB. In the first case, the ICB is severed on the one side of the MB, and the MB is inherited by the opposite daughter cell. In the second case, the MB is cut from both sides, expelled into the extracellular space, and later it can be engulfed by surrounding cells. Cells with lower autophagic activity, such as stem cells and cancer stem cells, are inclined to accumulate MBs. Inherited MBs affect cell polarity, modulate intra- and intercellular communication, enhance pluripotency of stem cells, and increase tumorigenic potential of cancer cells. In this review, we briefly summarize the latest knowledge on MB formation, inheritance, degradation, and function, and in addition, present and discuss our recent findings on the electrical and chemical communication of cells connected through the MB-containing ICB.

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