scholarly journals Fascetto interacting protein ensures proper cytokinesis and ploidy

2019 ◽  
Vol 30 (8) ◽  
pp. 992-1007 ◽  
Author(s):  
Zachary T. Swider ◽  
Rachel K. Ng ◽  
Ramya Varadarajan ◽  
Carey J. Fagerstrom ◽  
Nasser M. Rusan
Keyword(s):  
Cell Division ◽  
Tissue Repair ◽  
Complete Separation ◽  
Contractile Ring ◽  
Interacting Protein ◽  
Simultaneous Reduction ◽  
Central Spindle ◽  
Daughter Cells ◽  
Molecular Machinery ◽  
The Brain

Cell division is critical for development, organ growth, and tissue repair. The later stages of cell division include the formation of the microtubule (MT)-rich central spindle in anaphase, which is required to properly define the cell equator, guide the assembly of the acto-myosin contractile ring and ultimately ensure complete separation and isolation of the two daughter cells via abscission. Much is known about the molecular machinery that forms the central spindle, including proteins needed to generate the antiparallel overlapping interzonal MTs. One critical protein that has garnered great attention is the protein regulator of cytokinesis 1, or Fascetto (Feo) in Drosophila, which forms a homodimer to cross-link interzonal MTs, ensuring proper central spindle formation and cytokinesis. Here, we report on a new direct protein interactor and regulator of Feo we named Feo interacting protein (FIP). Loss of FIP results in a reduction in Feo localization, rapid disassembly of interzonal MTs, and several defects related to cytokinesis failure, including polyploidization of neural stem cells. Simultaneous reduction in Feo and FIP results in very large, tumorlike DNA-filled masses in the brain that contain hundreds of centrosomes. In aggregate, our data show that FIP acts directly on Feo to ensure fully accurate cell division.

scholarly journals Fascetto Interacting Protein (FIP) Regulates Fascetto (PRC1) to Ensure Proper Cytokinesis and Ploidy

2018 ◽  
Author(s):  
Zachary T. Swider ◽  
Rachel K. Ng ◽  
Ramya Varadarajan ◽  
Carey J. Fagerstrom ◽  
Nasser M Rusan
Keyword(s):  
Cell Division ◽  
Tissue Repair ◽  
Complete Separation ◽  
Contractile Ring ◽  
Interacting Protein ◽  
Simultaneous Reduction ◽  
Central Spindle ◽  
Daughter Cells ◽  
Molecular Machinery ◽  
The Brain

AbstractCell division is critical for development, organ growth, and tissue repair. The later stages of cell division include the formation of the microtubule (MT)-rich central spindle in anaphase, which is required to properly define the cell equator, guide the assembly of the acto-myosin contractile ring, and ultimately ensure complete separation and isolation of the two daughter cells via abscission. Much is known about the molecular machinery that forms the central spindle, including proteins needed to generate the antiparallel overlapping interzonal MTs. One critical protein that has garnered great attention is Protein Regulator of Cytokinesis 1 (PRC1), or Fascetto (Feo) in Drosophila, which forms a homodimer to crosslink interzonal MTs, ensuring proper central spindle formation and cytokinesis. Here, we report on a new direct protein interactor and regulator of Feo we named Fascetto Interacting Protein (FIP). Loss of FIP results in a significant reduction in Feo localization, rapid disassembly of interzonal MTs, and several cytokinesis defects. Simultaneous reduction in Feo and FIP results in tumor-like, DNA-filled masses in the brain. In aggregate our data show that FIP functions upstream of, and acts directly on, Feo to ensure fully accurate cell division.

scholarly journals Rap1-dependent pathways coordinate cytokinesis in Dictyostelium

2014 ◽  
Vol 25 (25) ◽  
pp. 4195-4204 ◽  
Author(s):  
Katarzyna Plak ◽  
Ineke Keizer-Gunnink ◽  
Peter J. M. van Haastert ◽  
Arjan Kortholt
Keyword(s):  
Cell Division ◽  
Cell Cortex ◽  
Adherent Cells ◽  
Contractile Ring ◽  
Daughter Cells ◽  
Small G Protein ◽  
Rap1 Activation ◽  
Actomyosin Cytoskeleton ◽  
Mutant Cells ◽  
Severe Growth

Cytokinesis is the final step of mitosis when a mother cell is separated into two daughter cells. Major cytoskeletal changes are essential for cytokinesis; it is, however, not well understood how the microtubules and actomyosin cytoskeleton are exactly regulated in time and space. In this paper, we show that during the early stages of cytokinesis, in rounded-up Dictyostelium discoideum cells, the small G-protein Rap1 is activated uniformly at the cell cortex. When cells begin to elongate, active Rap1 becomes restricted from the furrow region, where the myosin contractile ring is subsequently formed. In the final stages of cytokinesis, active Rap1 is only present at the cell poles. Mutant cells with decreased Rap1 activation at the poles showed strongly decreased growth rates. Hyperactivation of Rap1 results in severe growth delays and defective spindle formation in adherent cells and cell death in suspension. Furthermore, Rap mutants show aberrant regulation of the actomyosin cytoskeleton, resulting in extended furrow ingression times and asymmetrical cell division. We propose that Rap1 drives cytokinesis progression by coordinating the three major cytoskeletal components: microtubules, actin, and myosin II. Importantly, mutated forms of Rap also affect cytokinesis in other organisms, suggesting a conserved role for Rap in cell division.

scholarly journals The Cockayne syndrome group A and B proteins are part of a ubiquitin–proteasome degradation complex regulating cell division

2020 ◽  
Vol 117 (48) ◽  
pp. 30498-30508
Author(s):  
Elena Paccosi ◽  
Federico Costanzo ◽  
Michele Costantino ◽  
Alessio Balzerano ◽  
Laura Monteonofrio ◽  
...  
Keyword(s):  
Dna Repair ◽  
Cell Division ◽  
Degradation Process ◽  
Cockayne Syndrome ◽  
Intercellular Bridge ◽  
Proteasome Degradation ◽  
Daughter Cells ◽  
Multinucleated Cells ◽  
Ubiquitin Proteasome ◽  
Molecular Machinery

Cytokinesis is monitored by a molecular machinery that promotes the degradation of the intercellular bridge, a transient protein structure connecting the two daughter cells. Here, we found that CSA and CSB, primarily defined as DNA repair factors, are located at the midbody, a transient structure in the middle of the intercellular bridge, where they recruit CUL4 and MDM2 ubiquitin ligases and the proteasome. As a part of this molecular machinery, CSA and CSB contribute to the ubiquitination and the degradation of proteins such as PRC1, the Protein Regulator of Cytokinesis, to ensure the correct separation of the two daughter cells. Defects in CSA or CSB result in perturbation of the abscission leading to the formation of long intercellular bridges and multinucleated cells, which might explain part of the Cockayne syndrome phenotypes. Our results enlighten the role played by CSA and CSB as part of a ubiquitin/proteasome degradation process involved in transcription, DNA repair, and cell division.

scholarly journals The ARP2/3 complex prevents excessive formin activity during cytokinesis

2019 ◽  
Vol 30 (1) ◽  
pp. 96-107 ◽  
Author(s):  
Fung-Yi Chan ◽  
Ana M. Silva ◽  
Joana Saramago ◽  
Joana Pereira-Sousa ◽  
Hailey E. Brighton ◽  
...  
Keyword(s):  
Cell Division ◽  
Caenorhabditis Elegans ◽  
Actin Filament ◽  
Ring Formation ◽  
Contractile Ring ◽  
Present Evidence ◽  
Daughter Cells ◽  
Ring Constriction ◽  
Filament Network ◽  
Kinetics Of

Cytokinesis completes cell division by constriction of an actomyosin contractile ring that separates the two daughter cells. Here we use the early Caenorhabditis elegans embryo to explore how the actin filament network in the ring and the surrounding cortex is regulated by the single cytokinesis formin CYK-1 and the ARP2/3 complex, which nucleate nonbranched and branched filaments, respectively. We show that CYK-1 and the ARP2/3 complex are the predominant F-actin nucleators responsible for generating distinct cortical F-actin architectures and that depletion of either nucleator affects the kinetics of cytokinesis. CYK-1 is critical for normal F-actin levels in the contractile ring, and acute inhibition of CYK-1 after furrow ingression slows ring constriction rate, suggesting that CYK-1 activity is required throughout ring constriction. Surprisingly, although the ARP2/3 complex does not localize in the contractile ring, depletion of the ARP2 subunit or treatment with ARP2/3 complex inhibitor delays contractile ring formation and constriction. We present evidence that the delays are due to an excess in formin-nucleated cortical F-actin, suggesting that the ARP2/3 complex negatively regulates CYK-1 activity. We conclude that the kinetics of cytokinesis are modulated by interplay between the two major actin filament nucleators.

Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3164-3174 ◽  
Author(s):  
Larissa Lordier ◽  
Abdelali Jalil ◽  
Fréderic Aurade ◽  
Fréderic Larbret ◽  
Jerôme Larghero ◽  
...  
Keyword(s):  
Ploidy Level ◽  
Time Lapse ◽  
Polyploid Cell ◽  
Nonmuscle Myosin ◽  
Contractile Ring ◽  
Central Spindle ◽  
Daughter Cells ◽  
Late Failure ◽  
Pathway Activation ◽  
Spindle Elongation

Abstract Megakaryocyte (MK) is the naturally polyploid cell that gives rise to platelets. Polyploidization occurs by endomitosis, which was a process considered to be an incomplete mitosis aborted in anaphase. Here, we used time-lapse confocal video microscopy to visualize the endomitotic process of primary human megakaryocytes. Our results show that the switch from mitosis to endomitosis corresponds to a late failure of cytokinesis accompanied by a backward movement of the 2 daughter cells. No abnormality was observed in the central spindle of endomitotic MKs. A furrow formation was present, but the contractile ring was abnormal because accumulation of nonmuscle myosin IIA was lacking. In addition, a defect in cell elongation was observed in dipolar endomitotic MKs during telophase. RhoA and F-actin were partially concentrated at the site of furrowing. Inhibition of the Rho/Rock pathway caused the disappearance of F-actin at midzone and increased MK ploidy level. This inhibition was associated with a more pronounced defect in furrow formation as well as in spindle elongation. Our results suggest that the late failure of cytokinesis responsible for the endomitotic process is related to a partial defect in the Rho/Rock pathway activation.

scholarly journals Supervillin binding to myosin II and synergism with anillin are required for cytokinesis

2013 ◽  
Vol 24 (23) ◽  
pp. 3603-3619 ◽  
Author(s):  
Tara C. Smith ◽  
Peter C. Fridy ◽  
Yinyin Li ◽  
Shruti Basil ◽  
Sneha Arjun ◽  
...  
Keyword(s):  
Cell Division ◽  
Membrane Trafficking ◽  
Fluorescent Protein ◽  
Myosin Ii ◽  
Dominant Negative ◽  
Central Spindle ◽  
Daughter Cells ◽  
Interaction Partners ◽  
Green Fluorescent ◽  
Negative Phenotype

Cytokinesis, the process by which cytoplasm is apportioned between dividing daughter cells, requires coordination of myosin II function, membrane trafficking, and central spindle organization. Most known regulators act during late cytokinesis; a few, including the myosin II–binding proteins anillin and supervillin, act earlier. Anillin's role in scaffolding the membrane cortex with the central spindle is well established, but the mechanism of supervillin action is relatively uncharacterized. We show here that two regions within supervillin affect cell division: residues 831–1281, which bind central spindle proteins, and residues 1–170, which bind the myosin II heavy chain (MHC) and the long form of myosin light-chain kinase. MHC binding is required to rescue supervillin deficiency, and mutagenesis of this site creates a dominant-negative phenotype. Supervillin concentrates activated and total myosin II at the furrow, and simultaneous knockdown of supervillin and anillin additively increases cell division failure. Knockdown of either protein causes mislocalization of the other, and endogenous anillin increases upon supervillin knockdown. Proteomic identification of interaction partners recovered using a high-affinity green fluorescent protein nanobody suggests that supervillin and anillin regulate the myosin II and actin cortical cytoskeletons through separate pathways. We conclude that supervillin and anillin play complementary roles during vertebrate cytokinesis.

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.

scholarly journals Endosome mediated delivery of ceramide phosphoethanolamine (CPE) with unique acyl chain anchors to the cleavage furrow is essential for male meiosis cytokinesis

2021 ◽  
Author(s):  
Govind Kunduri ◽  
Si-Hung Le ◽  
Nagampalli Vijayakrishna ◽  
Daniel Blankenberg ◽  
Izumi Yoshihiro ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Acyl Chain ◽  
Structural Analog ◽  
Male Meiosis ◽  
Cleavage Furrow ◽  
Biophysical Properties ◽  
Contractile Ring ◽  
Central Spindle ◽  
Daughter Cells ◽  
Living Organisms

AbstractDivision of one cell into two daughter cells is fundamental in all living organisms. Cytokinesis, the final step of cell division, begins with the formation of an actomyosin contractile ring, positioned midway between the segregated chromosomes. Constriction of the ring with concomitant membrane deposition in a spatiotemporal precision generates a cleavage furrow that physically divides the cytoplasm. Unique lipids with specific biophysical properties have been shown to localize to midbodies however, their delivery mechanisms and biological roles were largely unknown. In this study, we show that Ceramide phosphoethanolamine (CPE), the structural analog of sphingomyelin, has unique acyl chain anchors in spermatocytes and is essential for meiosis cytokinesis. We found that disengagement of the central spindle from the contractile ring but not localization of phosphatidyl inositols (PIPs) at the plasma membrane was responsible for the male meiosis cytokinesis defect in CPE deficient animals. Further, we demonstrate that enrichment of CPE in Rab7 and Rab11 positive endosomes which in turn translocate to the cleavage furrows to promote cytokinesis. Our results implicate endosomal delivery of CPE to ingressing membranes is crucial for meiotic cytokinesis.

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.

Rab11 family-interacting protein 4, RAB11FIP4, is a differentially expressed gene in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Interacting Protein ◽  
Primary Tumors ◽  
Free Survival ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that Rab11 family-interacting protein 4, encoded by RAB11FIP4, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. RAB11FIP4 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of RAB11FIP4 in primary tumors was significantly correlated with patient recurrence-free survival and distant metastasis-free survival. Modulation of RAB11FIP4 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

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