scholarly journals ALIX and ESCRT-I/II function as parallel ESCRT-III recruiters in cytokinetic abscission

2016 ◽  
Vol 212 (5) ◽  
pp. 499-513 ◽  
Author(s):  
Liliane Christ ◽  
Eva M. Wenzel ◽  
Knut Liestøl ◽  
Camilla Raiborg ◽  
Coen Campsteijn ◽  
...  
Keyword(s):  
Cell Division ◽  
Final Stage ◽  
Binding Protein ◽  
Intercellular Bridge ◽  
Checkpoint Signaling ◽  
Endosomal Sorting ◽  
Daughter Cells ◽  
Escrt Machinery ◽  
Chromosome Bridges ◽  
In Cells

Cytokinetic abscission, the final stage of cell division where the two daughter cells are separated, is mediated by the endosomal sorting complex required for transport (ESCRT) machinery. The ESCRT-III subunit CHMP4B is a key effector in abscission, whereas its paralogue, CHMP4C, is a component in the abscission checkpoint that delays abscission until chromatin is cleared from the intercellular bridge. How recruitment of these components is mediated during cytokinesis remains poorly understood, although the ESCRT-binding protein ALIX has been implicated. Here, we show that ESCRT-II and the ESCRT-II–binding ESCRT-III subunit CHMP6 cooperate with ESCRT-I to recruit CHMP4B, with ALIX providing a parallel recruitment arm. In contrast to CHMP4B, we find that recruitment of CHMP4C relies predominantly on ALIX. Accordingly, ALIX depletion leads to furrow regression in cells with chromosome bridges, a phenotype associated with abscission checkpoint signaling failure. Collectively, our work reveals a two-pronged recruitment of ESCRT-III to the cytokinetic bridge and implicates ALIX in abscission checkpoint signaling.

scholarly journals The midbody ring scaffolds the abscission machinery in the absence of midbody microtubules

2013 ◽  
Vol 203 (3) ◽  
pp. 505-520 ◽  
Author(s):  
Rebecca A. Green ◽  
Jonathan R. Mayers ◽  
Shaohe Wang ◽  
Lindsay Lewellyn ◽  
Arshad Desai ◽  
...  
Keyword(s):  
Daughter Cell ◽  
Membrane Remodeling ◽  
Intercellular Bridge ◽  
Contractile Ring ◽  
Endosomal Sorting ◽  
Daughter Cells ◽  
Escrt Machinery ◽  
Two Stages ◽  
Inside Out

Abscission completes cytokinesis to form the two daughter cells. Although abscission could be organized from the inside out by the microtubule-based midbody or from the outside in by the contractile ring–derived midbody ring, it is assumed that midbody microtubules scaffold the abscission machinery. In this paper, we assess the contribution of midbody microtubules versus the midbody ring in the Caenorhabditis elegans embryo. We show that abscission occurs in two stages. First, the cytoplasm in the daughter cells becomes isolated, coincident with formation of the intercellular bridge; proper progression through this stage required the septins (a midbody ring component) but not the membrane-remodeling endosomal sorting complex required for transport (ESCRT) machinery. Second, the midbody and midbody ring are released into a specific daughter cell during the subsequent cell division; this stage required the septins and the ESCRT machinery. Surprisingly, midbody microtubules were dispensable for both stages. These results delineate distinct steps during abscission and highlight the central role of the midbody ring, rather than midbody microtubules, in their execution.

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.

scholarly journals The Abscission Checkpoint: A Guardian of Chromosomal Stability

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3350
Author(s):  
Eleni Petsalaki ◽  
George Zachos
Keyword(s):  
Mammalian Cells ◽  
Kinase Activity ◽  
Nuclear Pore ◽  
Aurora B ◽  
Intercellular Bridge ◽  
Endosomal Sorting ◽  
Daughter Cells ◽  
Chromosomal Passenger ◽  
Dividing Cells ◽  
Chromatin Bridges

The abscission checkpoint contributes to the fidelity of chromosome segregation by delaying completion of cytokinesis (abscission) when there is chromatin lagging in the intercellular bridge between dividing cells. Although additional triggers of an abscission checkpoint-delay have been described, including nuclear pore defects, replication stress or high intercellular bridge tension, this review will focus only on chromatin bridges. In the presence of such abnormal chromosomal tethers in mammalian cells, the abscission checkpoint requires proper localization and optimal kinase activity of the Chromosomal Passenger Complex (CPC)-catalytic subunit Aurora B at the midbody and culminates in the inhibition of Endosomal Sorting Complex Required for Transport-III (ESCRT-III) components at the abscission site to delay the final cut. Furthermore, cells with an active checkpoint stabilize the narrow cytoplasmic canal that connects the two daughter cells until the chromatin bridges are resolved. Unsuccessful resolution of chromatin bridges in checkpoint-deficient cells or in cells with unstable intercellular canals can lead to chromatin bridge breakage or tetraploidization by regression of the cleavage furrow. In turn, these outcomes can lead to accumulation of DNA damage, chromothripsis, generation of hypermutation clusters and chromosomal instability, which are associated with cancer formation or progression. Recently, many important questions regarding the mechanisms of the abscission checkpoint have been investigated, such as how the presence of chromatin bridges is signaled to the CPC, how Aurora B localization and kinase activity is regulated in late midbodies, the signaling pathways by which Aurora B implements the abscission delay, and how the actin cytoskeleton is remodeled to stabilize intercellular canals with DNA bridges. Here, we review recent progress toward understanding the mechanisms of the abscission checkpoint and its role in guarding genome integrity at the chromosome level, and consider its potential implications for cancer therapy.

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 chromosomal passenger complex controls the function of endosomal sorting complex required for transport-III Snf7 proteins during cytokinesis

Open Biology ◽  
2012 ◽  
Vol 2 (5) ◽  
pp. 120070 ◽  
Author(s):  
Luisa Capalbo ◽  
Emilie Montembault ◽  
Tetsuya Takeda ◽  
Zuni I. Bassi ◽  
David M. Glover ◽  
...  
Keyword(s):  
Cell Division ◽  
Molecular Basis ◽  
Cleavage Site ◽  
Human Cells ◽  
Membrane Association ◽  
Aurora B ◽  
Chromosomal Passenger Complex ◽  
Endosomal Sorting ◽  
Daughter Cells ◽  
Chromosomal Passenger

Summary Cytokinesis controls the proper segregation of nuclear and cytoplasmic materials at the end of cell division. The chromosomal passenger complex (CPC) has been proposed to monitor the final separation of the two daughter cells at the end of cytokinesis in order to prevent cell abscission in the presence of DNA at the cleavage site, but the precise molecular basis for this is unclear. Recent studies indicate that abscission could be mediated by the assembly of filaments comprising components of the endosomal sorting complex required for transport-III (ESCRT-III). Here, we show that the CPC subunit Borealin interacts directly with the Snf7 components of ESCRT-III in both Drosophila and human cells. Moreover, we find that the CPC's catalytic subunit, Aurora B kinase, phosphorylates one of the three human Snf7 paralogues—CHMP4C—in its C-terminal tail, a region known to regulate its ability to form polymers and associate with membranes. Phosphorylation at these sites appears essential for CHMP4C function because their mutation leads to cytokinesis defects. We propose that CPC controls abscission timing through inhibition of ESCRT-III Snf7 polymerization and membrane association using two concurrent mechanisms: interaction of its Borealin component with Snf7 proteins and phosphorylation of CHMP4C by Aurora B.

Cell Polarity and Migration: Emerging Role for the Endosomal Sorting Machinery

Physiology ◽  
2011 ◽  
Vol 26 (3) ◽  
pp. 171-180 ◽  
Author(s):  
Viola Hélène Lobert ◽  
Harald Stenmark
Keyword(s):  
Cell Migration ◽  
Cell Division ◽  
Cell Polarity ◽  
Tumor Suppressors ◽  
Potential Role ◽  
Endosomal Sorting ◽  
Escrt Machinery ◽  
Viral Budding ◽  
And Migration

The endosomal sorting complex required for transport (ESCRT) machinery has been implicated in the regulation of endosomal sorting, cell division, viral budding, autophagy, and cell signaling. Here, we review recent evidence that implicates ESCRTs in cell polarity and cell migration, and discuss the potential role of ESCRTs as tumor suppressors.

Inhibition of Cell Division by High External NaCl Concentrations in Synchronized Cultures of Chlorella emersonii

1982 ◽  
Vol 9 (2) ◽  
pp. 179 ◽  
Author(s):  
T.L Setter ◽  
H Greenway ◽  
J Kuo
Keyword(s):  
Electron Microscopy ◽  
Cell Division ◽  
Dna Synthesis ◽  
Dna Content ◽  
Cell Cycles ◽  
Daughter Cells ◽  
Specific Effects ◽  
Rna And Dna ◽  
Synchronized Cultures ◽  
In Cells

Effects of high external NaCl concentrations on growth were examined in the unicellular freshwater alga Cldorella emevsonii during different phases of cell development, using synchronized cultures obtained by alternating light-dark cycles. Growth of cultures synchronized at 1 mM NaCl [external osmotic pressure (next=) 0.08 MPa] was compared with (i) cultures synchronized at 200 mM NaCl (n,,, = 1.01 MPa) and (ii) cultures synchronized at 1 mM NaCl from which the daughter cells were suddenly transferred to 100, 150 or 200 mM NaCl. The effects of these two treatments on synthesis of protein, RNA and DNA during cell cycles were similar, and are attributed to the high nexta nd not to specific effects of Na+ and C1-. Growth inhibitions in cells at 200 mM NaCl relative to 1 mM NaCl occurred mainly via effects on cell division; this was confirmed by electron microscopy. There was a lag before net DNA synthesis commenced, and there were reductions in rates of net DNA synthesis in cells at 200 mM NaCl relative to 1 mM NaC1. Rates of increase in cell volume and in protein and RNA content per cell were little affected by high external NaCl concentrations. Consequently, daughter cells at 200 mM NaCl were approximately twice the volume and contained twice as much protein and RNA as daughter cells at 1 mM NaCl, while DNA content was equal in daughter cells at 1 and 200 mM NaCl.

scholarly journals Secreted midbody remnants are a class of extracellular vesicles molecularly distinct from exosomes and microparticles

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Alin Rai ◽  
David W. Greening ◽  
Rong Xu ◽  
Maoshan Chen ◽  
Wittaya Suwakulsiri ◽  
...  
Keyword(s):  
Cell Division ◽  
Large Scale ◽  
Cellular Transformation ◽  
Extracellular Vesicle ◽  
Colon Cancer Cells ◽  
Intercellular Bridge ◽  
Extracellular Medium ◽  
Daughter Cells ◽  
Biochemical Characterisation ◽  
Sister Cells

AbstractDuring the final stages of cell division, newly-formed daughter cells remain connected by a thin intercellular bridge containing the midbody (MB), a microtubule-rich organelle responsible for cytokinetic abscission. Following cell division the MB is asymmetrically inherited by one daughter cell where it persists as a midbody remnant (MB-R). Accumulating evidence shows MB-Rs are secreted (sMB-Rs) into the extracellular medium and engulfed by neighbouring non-sister cells. While much is known about intracellular MB-Rs, sMB-Rs are poorly understood. Here, we report the large-scale purification and biochemical characterisation of sMB-Rs released from colon cancer cells, including profiling of their proteome using mass spectrometry. We show sMB-Rs are an abundant class of membrane-encapsulated extracellular vesicle (200-600 nm) enriched in core cytokinetic proteins and molecularly distinct from exosomes and microparticles. Functional dissection of sMB-Rs demonstrated that they are engulfed by, and accumulate in, quiescent fibroblasts where they promote cellular transformation and an invasive phenotype.

scholarly journals Kinesin-Binding Protein (KBP) buffers the activity of KIF18A and KIF15 in mitosis to ensure accurate chromosome segregation

2018 ◽  
Author(s):  
Heidi L. H. Malaby ◽  
Megan E. Dumas ◽  
Ryoma Ohi ◽  
Jason Stumpff
Keyword(s):  
Motor Activity ◽  
Chromosome Segregation ◽  
Binding Protein ◽  
Mitotic Chromosomes ◽  
Microtubule Binding ◽  
Daughter Cells ◽  
Chromosome Alignment ◽  
Segregation Of Chromosomes ◽  
In Cells

ABSTRACTMitotic kinesins must be regulated to ensure a precise balance of spindle forces and accurate segregation of chromosomes into daughter cells. Here we demonstrate that Kinesin-Binding Protein (KBP) reduces the activity of KIF18A and KIF15 during metaphase. Overexpression of KBP disrupts the movement and alignment of mitotic chromosomes and decreases spindle length, a combination of phenotypes observed in cells deficient for KIF18A and KIF15, respectively. We show through gliding filament and microtubule co-pelleting assays that KBP directly inhibits KIF18A and KIF15 motor activity by preventing microtubule-binding. Consistent with these effects, the mitotic localizations of KIF18A and KIF15 are altered by overexpression of KBP. Cells depleted of KBP exhibit lagging chromosomes in anaphase, an effect that is recapitulated by KIF15 and KIF18A overexpression. Based on these data, we propose a model in which KBP acts as a protein buffer in mitosis, protecting cells from excessive KIF18A and KIF15 activity to promote accurate chromosome segregation.SUMMARYKinesin-Binding Protein (KBP) is identified as a regulator of the kinesins KIF18A and KIF15 during mitosis. KBP buffers the activity of these motors to control chromosome alignment and spindle integrity in metaphase and prevent lagging chromosomes in anaphase.

scholarly journals ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Anna Caballe ◽  
Dawn M Wenzel ◽  
Monica Agromayor ◽  
Steven L Alam ◽  
Jack J Skalicky ◽  
...  
Keyword(s):  
Nuclear Pore ◽  
Aurora B ◽  
Physical Separation ◽  
Protection Mechanism ◽  
Endosomal Sorting ◽  
Daughter Cells ◽  
Escrt Machinery ◽  
A Genome ◽  
Biochemical Studies ◽  
Genome Protection

The endosomal sorting complexes required for transport (ESCRT) machinery mediates the physical separation between daughter cells during cytokinetic abscission. This process is regulated by the abscission checkpoint, a genome protection mechanism that relies on Aurora B and the ESCRT-III subunit CHMP4C to delay abscission in response to chromosome missegregation. In this study, we show that Unc-51-like kinase 3 (ULK3) phosphorylates and binds ESCRT-III subunits via tandem MIT domains, and thereby, delays abscission in response to lagging chromosomes, nuclear pore defects, and tension forces at the midbody. Our structural and biochemical studies reveal an unusually tight interaction between ULK3 and IST1, an ESCRT-III subunit required for abscission. We also demonstrate that IST1 phosphorylation by ULK3 is an essential signal required to sustain the abscission checkpoint and that ULK3 and CHMP4C are functionally linked components of the timer that controls abscission in multiple physiological situations.

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