scholarly journals GTSE1 regulates spindle microtubule dynamics to control Aurora B kinase and Kif4A chromokinesin on chromosome arms

2017 ◽  
Vol 216 (10) ◽  
pp. 3117-3132 ◽  
Author(s):  
Aaron R. Tipton ◽  
Jonathan D. Wren ◽  
John R. Daum ◽  
Joseph C. Siefert ◽  
Gary J. Gorbsky
Keyword(s):  
Mitotic Spindle ◽  
Meta Analysis ◽  
Metaphase Plate ◽  
Spindle Pole ◽  
Aurora B ◽  
Chromosome Movement ◽  
Aurora B Kinase ◽  
Nuclear Envelope Breakdown ◽  
M Phase ◽  
Spindle Microtubules

In mitosis, the dynamic assembly and disassembly of microtubules are critical for normal chromosome movement and segregation. Microtubule turnover varies among different mitotic spindle microtubules, dictated by their spatial distribution within the spindle. How turnover among the various classes of spindle microtubules is differentially regulated and the resulting significance of differential turnover for chromosome movement remains a mystery. As a new tactic, we used global microarray meta-analysis (GAMMA), a bioinformatic method, to identify novel regulators of mitosis, and in this study, we describe G2- and S phase–expressed protein 1 (GTSE1). GTSE1 is expressed exclusively in late G2 and M phase. From nuclear envelope breakdown until anaphase onset, GTSE1 binds preferentially to the most stable mitotic spindle microtubules and promotes their turnover. Cells depleted of GTSE1 show defects in chromosome alignment at the metaphase plate and in spindle pole integrity. These defects are coupled with an increase in the proportion of stable mitotic spindle microtubules. A consequence of this reduced microtubule turnover is diminished recruitment and activity of Aurora B kinase on chromosome arms. This decrease in Aurora B results in diminished binding of the chromokinesin Kif4A to chromosome arms.

scholarly journals A comparison of the distribution of actin and tubulin in the mammalian mitotic spindle as seen by indirect immunofluorescence.

1977 ◽  
Vol 72 (3) ◽  
pp. 552-567 ◽  
Author(s):  
W Z Cande ◽  
E Lazarides ◽  
J R McIntosh
Keyword(s):  
Indirect Immunofluorescence ◽  
Mitotic Spindle ◽  
Metaphase Plate ◽  
Spindle Pole ◽  
Early Prophase ◽  
Chromosome Movement ◽  
Late Prophase ◽  
Small Ball ◽  
Nuclear Envelope Breakdown ◽  
Daughter Cells

Rabbit antibodies against actin and tubulin were used in an indirect immunofluorescence study of the structure of the mitotic spindle of PtK1 cells after lysis under conditions that preserve anaphase chromosome movement. During early prophase there is no antiactin staining associated with the mitotic centers, but by late prophase, as the spindle is beginning to form, a small ball of actin antigenicity is found beside the nucleus; After nuclear envelope breakdown, the actiactin stains the region around each mitotic center, and becomes organized into fibers that run between the chromosomes and the poles. Colchicine blocks this organization, but does not disrupt the staining at the poles. At metaphase the antiactin reveals a halo of ill-defined radius around each spindle pole and fibers that run from the poles to the metaphase plate. Antitubulin shows astral rays, fibers running from chromosomes to poles, and some fibers that run across the metaphase plate. At anaphase, there is a shortening of the antiactin-stained fibers, leaving a zone which is essentially free of actin-staining fluorescence between the separating chromosomes. Antitubulin stains the region between chromosomes and poles, but also reveals substantial fibers running through the zone between separating chromosomes. Cells fixed during cytokinesis show actin in the region of the cleavage furrow, while antitubulin reveals the fibrous spindle remnant that runs between daughter cells. These results suggest that actin is a component of the mammalian mitotic spindle, that the distribution of actin differs from that of tubulin and that the distributions of these two fibrous proteins change in different ways during anaphase.

Regulation of kinetochore–microtubule attachments by Aurora B kinase

2009 ◽  
Vol 37 (5) ◽  
pp. 976-980 ◽  
Author(s):  
Dan Liu ◽  
Michael A. Lampson
Keyword(s):  
Opposite Direction ◽  
Mitotic Spindle ◽  
Present Review ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Spindle Microtubules ◽  
Segregation Of Chromosomes

Accurate segregation of chromosomes in mitosis requires that spindle microtubules attach sister kinetochores to opposite poles of the mitotic spindle (biorientation). To achieve biorientation of all chromosomes, incorrect attachments are selectively destabilized, providing a fresh opportunity to biorient, whereas correct attachments are stabilized. Tension across the centromere may be the signal that distinguishes different attachment states, as spindle microtubules pull bioriented sister kinetochores in the opposite direction. Destabilization of incorrect attachments requires the Ipl1/Aurora B kinase, which phosphorylates kinetochore substrates that directly interact with microtubules. The present review focuses on how Aurora B regulates attachments in response to centromere tension.

Correlative Video Light, Immunofluorescence, and Electron Microscopy of Chromosome Attachment to the Forming Vertebrate Spindle: Implications for Force Production During Mitosis

1990 ◽  
Vol 48 (3) ◽  
pp. 192-193
Author(s):  
Conly L. Rieder ◽  
Stephen P. Alexander ◽  
John Hayden ◽  
Samuel S. Bowser
Keyword(s):  
Mitotic Spindle ◽  
Force Production ◽  
Cell Types ◽  
Chromosome Movement ◽  
Nuclear Envelope Breakdown ◽  
Molecular Force ◽  
Keratin Filaments ◽  
Chromosome Attachment ◽  
Spindle Microtubules ◽  
Chromosome Motion

This abstract summarizes a number of recently published observations from this laboratory on the formation of the mitotic spindle (1-3), and on the dynamic behavior of spindle microtubules (4).Since chromosome movement during mitosis is, for the most part, directed towards a pole the emphasis of most mitosis research is to elucidate the molecular force-producing mechanism(s) behind this movement. Past studies reveal that poleward chromosome motion is dependent on the attachment of spindle microtubules (MTs) to the kinetochore of the chromosome. However, the origin of these MTs and their role in force production remain controversial. It is similarly unclear whether prometaphase and anaphase chromosomes are moved by the same, or a different, force-producing mechanism(s).The mitotic spindle of cultured newt (T. granulosa) pneumocytes forms in an optically clear region of cytoplasm defined by a cage of keratin filaments (1). As in other cell types possessing an astral spindle, chromosomes in newt pneumocytes that are positioned closer to one pole at nuclear envelope breakdown initially form a monopolar attachment to, and move towards, that pole.

Fyn Accelerates M Phase Progression by Promoting the Assembly of Mitotic Spindle Microtubules

2015 ◽  
Vol 117 (4) ◽  
pp. 894-903 ◽  
Author(s):  
Mai Okamoto ◽  
Yuji Nakayama ◽  
Ayana Kakihana ◽  
Ryuzaburo Yuki ◽  
Noritaka Yamaguchi ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
M Phase ◽  
Phase Progression ◽  
Spindle Microtubules

scholarly journals The right place at the right time: Aurora B kinase localization to centromeres and kinetochores

2020 ◽  
Vol 64 (2) ◽  
pp. 299-311 ◽  
Author(s):  
Amanda J. Broad ◽  
Jennifer G. DeLuca
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Protein Complexes ◽  
Centromeric Heterochromatin ◽  
Aurora B ◽  
Mitotic Chromosomes ◽  
Large Protein ◽  
Aurora B Kinase ◽  
Centromeric Protein ◽  
Spindle Microtubules ◽  
The Right

Abstract The fidelity of chromosome segregation during mitosis is intimately linked to the function of kinetochores, which are large protein complexes assembled at sites of centromeric heterochromatin on mitotic chromosomes. These key “orchestrators” of mitosis physically connect chromosomes to spindle microtubules and transduce forces through these connections to congress chromosomes and silence the spindle assembly checkpoint. Kinetochore-microtubule attachments are highly regulated to ensure that incorrect attachments are not prematurely stabilized, but instead released and corrected. The kinase activity of the centromeric protein Aurora B is required for kinetochore-microtubule destabilization during mitosis, but how the kinase acts on outer kinetochore substrates to selectively destabilize immature and erroneous attachments remains debated. Here, we review recent literature that sheds light on how Aurora B kinase is recruited to both centromeres and kinetochores and discuss possible mechanisms for how kinase interactions with substrates at distinct regions of mitotic chromosomes are regulated.

The role of gamma-tubulin in mitotic spindle formation and cell cycle progression in Aspergillus nidulans

1997 ◽  
Vol 110 (5) ◽  
pp. 623-633 ◽  
Author(s):  
M.A. Martin ◽  
S.A. Osmani ◽  
B.R. Oakley
Keyword(s):  
Cell Cycle ◽  
Mitotic Spindle ◽  
Cell Cycle Progression ◽  
Spindle Pole ◽  
Microtubule Assembly ◽  
Cytoplasmic Microtubule ◽  
Cycle Progression ◽  
Spindle Microtubules ◽  
Gamma Tubulin

gamma-Tubulin has been hypothesized to be essential for the nucleation of the assembly of mitotic spindle microtubules, but some recent results suggest that this may not be the case. To clarify the role of gamma-tubulin in microtubule assembly and cell-cycle progression, we have developed a novel variation of the gene disruption/heterokaryon rescue technique of Aspergillus nidulans. We have used temperature-sensitive cell-cycle mutations to synchronize germlings carrying a gamma-tubulin disruption and observe the phenotypes caused by the disruption in the first cell cycle after germination. Our results indicate that gamma-tubulin is absolutely required for the assembly of mitotic spindle microtubules, a finding that supports the hypothesis that gamma-tubulin is involved in spindle microtubule nucleation. In the absence of functional gamma-tubulin, nuclei are blocked with condensed chromosomes for about the length of one cell cycle before chromatin decondenses without nuclear division. Our results indicate that gamma-tubulin is not essential for progression from G1 to G2, for entry into mitosis nor for spindle pole body replication. It is also not required for reactivity of spindle pole bodies with the MPM-2 antibody which recognizes a phosphoepitope important to mitotic spindle formation. Finally, it does not appear to be absolutely required for cytoplasmic microtubule assembly but may play a role in the formation of normal cytoplasmic microtubule arrays.

scholarly journals Mitotic spindle disassembly occurs via distinct subprocesses driven by the anaphase-promoting complex, Aurora B kinase, and kinesin-8

2010 ◽  
Vol 191 (4) ◽  
pp. 795-808 ◽  
Author(s):  
Jeffrey B. Woodruff ◽  
David G. Drubin ◽  
Georjana Barnes
Keyword(s):  
Mitotic Spindle ◽  
Cell Cycle Progression ◽  
Dynamic Structure ◽  
Aurora B ◽  
Anaphase Promoting Complex ◽  
Microtubule Depolymerization ◽  
Aurora B Kinase ◽  
Synthetic Lethal ◽  
Spindle Disassembly ◽  
Spindle Elongation

The mitotic spindle is a complex and dynamic structure. Although much has been learned about how spindles assemble and mediate chromosome segregation, how spindles rapidly and irreversibly disassemble during telophase is less clear. We used synthetic lethal screens in budding yeast to identify mutants defective in spindle disassembly. Real-time, live cell imaging analysis of spindle disassembly was performed on nine mutants defective in this process. Results of this analysis suggest that spindle disassembly is achieved by mechanistically distinct but functionally overlapping subprocesses: disengagement of the spindle halves, arrest of spindle elongation, and initiation of interpolar microtubule depolymerization. These subprocesses are largely governed by the anaphase-promoting complex, Aurora B kinase, and kinesin-8. Combinatorial inhibition of these subprocesses yielded cells with hyperstable spindle remnants and dramatic defects in cell cycle progression, establishing that rapid spindle disassembly is crucial for cell proliferation.

scholarly journals Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly

2008 ◽  
Vol 181 (2) ◽  
pp. 241-254 ◽  
Author(s):  
Michael J. Emanuele ◽  
Weijie Lan ◽  
Miri Jwa ◽  
Stephanie A. Miller ◽  
Clarence S.M. Chan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Phosphatase ◽  
Protein Phosphatase 1 ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Culture Cells ◽  
Kinetochore Assembly ◽  
M Phase ◽  
Egg Extracts ◽  
Cycle Dependent

The outer kinetochore binds microtubules to control chromosome movement. Outer kinetochore assembly is restricted to mitosis, whereas the inner kinetochore remains tethered to centromeres throughout the cell cycle. The cues that regulate this transient assembly are unknown. We find that inhibition of Aurora B kinase significantly reduces outer kinetochore assembly in Xenopus laevis and human tissue culture cells, frog egg extracts, and budding yeast. In X. leavis M phase extracts, preassembled kinetochores disassemble after inhibiting Aurora B activity with either drugs or antibodies. Kinetochore disassembly, induced by Aurora B inhibition, is rescued by restraining protein phosphatase 1 (PP1) activity. PP1 is necessary for kinetochores to disassemble at the exit from M phase, and purified enzyme is sufficient to cause disassembly on isolated mitotic nuclei. These data demonstrate that Aurora B activity is required for kinetochore maintenance and that PP1 is necessary and sufficient to disassemble kinetochores. We suggest that Aurora B and PP1 coordinate cell cycle–dependent changes in kinetochore assembly though phosphorylation of kinetochore substrates.

scholarly journals Contractile acto-myosin network on nuclear envelope remnants positions human chromosomes for mitosis

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Alexander JR Booth ◽  
Zuojun Yue ◽  
John K Eykelenboom ◽  
Tom Stiff ◽  
GW Gant Luxton ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Mitotic Spindle ◽  
Dependent Manner ◽  
Linc Complex ◽  
Nuclear Envelope Breakdown ◽  
Cytoplasmic Surface ◽  
Chromosome Congression ◽  
Spindle Microtubules ◽  
Scattering Volume ◽  
Early Mitosis

To ensure proper segregation during mitosis, chromosomes must be efficiently captured by spindle microtubules and subsequently aligned on the mitotic spindle. The efficacy of chromosome interaction with the spindle can be influenced by how widely chromosomes are scattered in space. Here, we quantify chromosome-scattering volume (CSV) and find that it is reduced soon after nuclear envelope breakdown (NEBD) in human cells. The CSV reduction occurs primarily independently of microtubules and is therefore not an outcome of interactions between chromosomes and the spindle. We find that, prior to NEBD, an acto-myosin network is assembled in a LINC complex-dependent manner on the cytoplasmic surface of the nuclear envelope. This acto-myosin network remains on nuclear envelope remnants soon after NEBD, and its myosin-II-mediated contraction reduces CSV and facilitates timely chromosome congression and correct segregation. Thus, we find a novel mechanism that positions chromosomes in early mitosis to ensure efficient and correct chromosome–spindle interactions.

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