scholarly journals Both midzone and astral microtubules are involved in the delivery of cytokinesis signals

2002 ◽  
Vol 159 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Maki Murata-Hori ◽  
Yu-li Wang
Keyword(s):  
Signaling Pathway ◽  
Cultured Cells ◽  
Aurora B ◽  
Anaphase Onset ◽  
Cytoplasmic Proteins ◽  
Chromosomal Passenger ◽  
Dynamic Exchange ◽  
Passenger Protein

To address the mechanism that coordinates cytokinesis with mitosis, we have studied the dynamics of aurora B, a chromosomal passenger protein involved in signaling cytokinesis. Photobleaching analyses indicated dynamic exchange of aurora B between a centromeric and a cytoplasmic pool before anaphase onset, and stable associations with microtubules after anaphase onset. Bleaching near centromeres upon anaphase onset affected the subsequent appearance of fluorescence along midzone microtubules, but not that near the lateral equatorial cortex, suggesting that there were centromeric-dependent and -independent pathways that transported aurora B to the equator. The former delivered centromeric aurora B along midzone microtubules, whereas the latter delivered cytoplasmic aurora B along astral microtubules. We suggest that cultured cells use midzone microtubules as the primary signaling pathway for cytokinesis, whereas embryos, with their stockpile of cytoplasmic proteins and large sizes, rely primarily on astral microtubules.

scholarly journals Use of DT40 conditional-knockout cell lines to study chromosomal passenger protein function

2010 ◽  
Vol 38 (6) ◽  
pp. 1655-1659 ◽  
Author(s):  
Xavier Fant ◽  
Kumiko Samejima ◽  
Ana Carvalho ◽  
Hiromi Ogawa ◽  
Zhenjie Xu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Protein Function ◽  
Kinase Activity ◽  
Current Knowledge ◽  
Conditional Knockout ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Chromosomal Passenger ◽  
Passenger Protein

The CPC [chromosomal passenger complex; INCENP (inner centromere protein), Aurora B kinase, survivin and borealin] is implicated in many mitotic processes. In the present paper we describe how we generated DT40 conditional-knockout cell lines for incenp1 and survivin1 to better understand the role of these CPC subunits in the control of Aurora B kinase activity. These lines enabled us to reassess current knowledge of survivin function and to show that INCENP acts as a rheostat for Aurora B activity.

The role of centromere-binding factor 3 (CBF3) in spindle stability, cytokinesis, and kinetochore attachment

2005 ◽  
Vol 83 (6) ◽  
pp. 696-702 ◽  
Author(s):  
David Bouck ◽  
Kerry Bloom
Keyword(s):  
Essential Role ◽  
Anaphase Onset ◽  
Binding Factor ◽  
Chromosomal Passenger ◽  
Chromosomal Passenger Proteins ◽  
Spindle Midzone ◽  
Spindle Stability ◽  
Passenger Proteins ◽  
Passenger Protein

The spindle midzone is critical for spindle stability and cytokinesis. Chromosomal passenger proteins relocalize from chromosomes to the spindle midzone after anaphase onset. The recent localization of the inner-kinetochore, centromere-binding factor 3 (CBF3) complex to the spindle midzone in budding yeast has led to the discovery of novel functions for this complex in addition to its essential role at kinetochores. In G1/S cells, CBF3 components are detected along dynamic microtubules, where they can "search-and-capture" newly replicated centromeres. During anaphase, CBF3 is transported to the microtubule plus-ends of the spindle midzone. Consistent with this localization, cells containing a mutation in the CBF3 subunit Ndc10p show defects in spindle stability during anaphase. In addition, ndc10-1 cells show defects during cytokinesis, resulting in a defect in cell abscission. These results highlight the importance of midzone-targeted proteins in coordinating mitosis with cell division. Here we discuss these findings and explore the significance of CBF3 transport to microtubule plus-ends at the spindle midzone.Key words: spindle midzone, passenger protein, inner centromere protein (INCENP), microtubule plus-end.

Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells

2004 ◽  
Vol 59 (4) ◽  
pp. 249-263 ◽  
Author(s):  
Kaori Sasai ◽  
Hiroshi Katayama ◽  
David L. Stenoien ◽  
Satoshi Fujii ◽  
Reiko Honda ◽  
...  
Keyword(s):  
Aurora B ◽  
Aurora B Kinase ◽  
Chromosomal Passenger ◽  
Passenger Protein ◽  
Mitotic Cells

scholarly journals Probing the Dynamics and Functions of Aurora B Kinase in Living Cells during Mitosis and Cytokinesis

2002 ◽  
Vol 13 (4) ◽  
pp. 1099-1108 ◽  
Author(s):  
Maki Murata-Hori ◽  
Masaaki Tatsuka ◽  
Yu-Li Wang
Keyword(s):  
Kinase Activity ◽  
Fluorescent Protein ◽  
Aurora B ◽  
Anaphase Onset ◽  
Abnormal Mitosis ◽  
Chromosomal Passenger ◽  
Early Anaphase ◽  
Dividing Cells ◽  
Spindle Midzone ◽  
Green Fluorescent

Aurora B is a protein kinase and a chromosomal passenger protein that undergoes dynamic redistribution during mitosis. We have probed the mechanism that regulates its localization with cells expressing green fluorescent protein (GFP)-tagged wild-type or mutant aurora B. Aurora B was found at centromeres at prophase and persisted until ∼0.5 min after anaphase onset, when it redistributed to the spindle midzone and became concentrated at the equator along midzone microtubules. Depolymerization of microtubules inhibited the dissociation of aurora B from centromeres at early anaphase and caused the dispersion of aurora B from the spindle midzone at late anaphase; however, centromeric association during prometaphase was unaffected. Inhibition of CDK1 deactivation similarly caused aurora B to remain associated with centromeres during anaphase. In contrast, inhibition of the kinase activity of aurora B appeared to have no effect on its interactions with centromeres or initial relocation onto midzone microtubules. Instead, kinase-inactive aurora B caused abnormal mitosis and deactivation of the spindle checkpoint. In addition, midzone microtubule bundles became destabilized and aurora B dispersed from the equator. Our results suggest that microtubules, CDK1, and the kinase activity each play a distinct role in the dynamics and functions of aurora B in dividing cells.

Evidence for cGAS-STING signaling in the female genital tract resistance to Chlamydia trachomatis infection

2022 ◽  
Author(s):  
Xin Su ◽  
Hong Xu ◽  
Maegan French ◽  
Yujie Zhao ◽  
Lingli Tang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Chlamydia Trachomatis ◽  
Signaling Pathway ◽  
Genital Tract ◽  
Essential Role ◽  
Cultured Cells ◽  
Female Genital Tract ◽  
Lower Genital Tract ◽  
Female Genital

Sexually transmitted Chlamydia trachomatis can ascend to the upper genital tract due to its resistance to innate immunity in the lower genital tract. C. trachomatis can activate cGAS-STING signaling pathway in cultured cells via either cGAS or STING. The current study was designed to evaluate the role of the cGAS-STING pathway in innate immunity against C. trachomatis in the mouse genital tract. Following intravaginal inoculation, C. trachomatis significantly declined by day 5 following a peak infection on day 3 while the mouse-adapted C. muridarum continued to rise for >1 week, indicating that C. trachomatis is susceptible to the innate immunity in the female mouse genital tract. This conclusion was supported by the observation of a similar shedding course in mice deficient in adaptive immunity. Thus, C. trachomatis can be used to evaluate innate immunity in the female genital tract. It was found that mice deficient in either cGAS or STING significantly increased the yields of live C. trachomatis on day 5, indicating an essential role of the cGAS-STING signaling pathway in innate immunity of the mouse genital tract. Comparison of live C. trachomatis recovered from different genital tissues revealed that the cGAS-STING-dependent immunity against C. trachomatis was restricted to the mouse lower genital tract regardless of whether C. trachomatis was inoculated intravaginally or transcervically. Thus, we have demonstrated an essential role of the cGAS-STING signaling pathway in innate immunity against chlamydial infection, laying a foundation for further illuminating the mechanisms of the innate immunity in the female lower genital tract.

scholarly journals Differential requirement for Bub1 and Bub3 in regulation of meiotic versus mitotic chromosome segregation

2020 ◽  
Vol 219 (4) ◽  
Author(s):  
Gisela Cairo ◽  
Anne M. MacKenzie ◽  
Soni Lacefield
Keyword(s):  
Chromosome Segregation ◽  
Protein Phosphatase ◽  
Mitotic Chromosome ◽  
Budding Yeast ◽  
Meiotic Chromosome ◽  
Protein Phosphatase 1 ◽  
Aurora B ◽  
Chromosome Missegregation ◽  
Anaphase Onset ◽  
Spindle Microtubules

Accurate chromosome segregation depends on the proper attachment of kinetochores to spindle microtubules before anaphase onset. The Ipl1/Aurora B kinase corrects improper attachments by phosphorylating kinetochore components and so releasing aberrant kinetochore–microtubule interactions. The localization of Ipl1 to kinetochores in budding yeast depends upon multiple pathways, including the Bub1–Bub3 pathway. We show here that in meiosis, Bub3 is crucial for correction of attachment errors. Depletion of Bub3 results in reduced levels of kinetochore-localized Ipl1 and concomitant massive chromosome missegregation caused by incorrect chromosome–spindle attachments. Depletion of Bub3 also results in shorter metaphase I and metaphase II due to premature localization of protein phosphatase 1 (PP1) to kinetochores, which antagonizes Ipl1-mediated phosphorylation. We propose a new role for the Bub1–Bub3 pathway in maintaining the balance between kinetochore localization of Ipl1 and PP1, a balance that is essential for accurate meiotic chromosome segregation and timely anaphase onset.

scholarly journals The Ki-67 and RepoMan mitotic phosphatases assemble via an identical, yet novel mechanism

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Ganesan Senthil Kumar ◽  
Ezgi Gokhan ◽  
Sofie De Munter ◽  
Mathieu Bollen ◽  
Paola Vagnarelli ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Mitotic Chromosome ◽  
Cancer Therapeutics ◽  
Mitotic Exit ◽  
Protein Phosphatase 1 ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Ki 67 ◽  
Anaphase Onset

Ki-67 and RepoMan have key roles during mitotic exit. Previously, we showed that Ki-67 organizes the mitotic chromosome periphery and recruits protein phosphatase 1 (PP1) to chromatin at anaphase onset, in a similar manner as RepoMan (<xref ref-type="bibr" rid="bib2">Booth et al., 2014</xref>). Here we show how Ki-67 and RepoMan form mitotic exit phosphatases by recruiting PP1, how they distinguish between distinct PP1 isoforms and how the assembly of these two holoenzymes are dynamically regulated by Aurora B kinase during mitosis. Unexpectedly, our data also reveal that Ki-67 and RepoMan bind PP1 using an identical, yet novel mechanism, interacting with a PP1 pocket that is engaged only by these two PP1 regulators. These findings not only show how two distinct mitotic exit phosphatases are recruited to their substrates, but also provide immediate opportunities for the design of novel cancer therapeutics that selectively target the Ki-67:PP1 and RepoMan:PP1 holoenzymes.

scholarly journals VBP1 modulates Wnt/β-catenin signaling by mediating the stability of the transcription factors TCF/LEFs

2020 ◽  
Vol 295 (49) ◽  
pp. 16826-16839
Author(s):  
Haifeng Zhang ◽  
Xiaozhi Rong ◽  
Caixia Wang ◽  
Yunzhang Liu ◽  
Ling Lu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Protein Stability ◽  
Signaling Pathway ◽  
Cultured Cells ◽  
Critical Role ◽  
Family Members ◽  
Von Hippel Lindau ◽  
T Cell Factor ◽  
Protein Levels ◽  
The Stability

The Wnt/β-catenin pathway is one of the major pathways that regulates embryonic development, adult homeostasis, and stem cell self-renewal. In this pathway, transcription factors T-cell factor and lymphoid enhancer factor (TCF/LEF) serve as a key switch to repress or activate Wnt target gene transcription by recruiting repressor molecules or interacting with the β-catenin effector, respectively. It has become evident that the protein stability of the TCF/LEF family members may play a critical role in controlling the activity of the Wnt/β-catenin signaling pathway. However, factors that regulate the stability of TCF/LEFs remain largely unknown. Here, we report that pVHL binding protein 1 (VBP1) regulates the Wnt/β-catenin signaling pathway by controlling the stability of TCF/LEFs. Surprisingly, we found that either overexpression or knockdown of VBP1 decreased Wnt/β-catenin signaling activity in both cultured cells and zebrafish embryos. Mechanistically, VBP1 directly binds to all four TCF/LEF family members and von Hippel-Lindau tumor-suppressor protein (pVHL). Either overexpression or knockdown of VBP1 increases the association between TCF/LEFs and pVHL and then decreases the protein levels of TCF/LEFs via proteasomal degradation. Together, our results provide mechanistic insights into the roles of VBP1 in controlling TCF/LEFs protein stability and regulating Wnt/β-catenin signaling pathway activity.

scholarly journals PLK1 plays dual roles in centralspindlin regulation during cytokinesis

2019 ◽  
Vol 218 (4) ◽  
pp. 1250-1264 ◽  
Author(s):  
Ingrid E. Adriaans ◽  
Angika Basant ◽  
Bas Ponsioen ◽  
Michael Glotzer ◽  
Susanne M.A. Lens
Keyword(s):  
Small Gtpase ◽  
The Other ◽  
Aurora B ◽  
Cleavage Furrow ◽  
Contractile Ring ◽  
Dual Roles ◽  
Early Step ◽  
Rhoa Activation ◽  
Anaphase Onset ◽  
Spindle Midzone

Cytokinesis begins upon anaphase onset. An early step involves local activation of the small GTPase RhoA, which triggers assembly of an actomyosin-based contractile ring at the equatorial cortex. Here, we delineated the contributions of PLK1 and Aurora B to RhoA activation and cytokinesis initiation in human cells. Knock-down of PRC1, which disrupts the spindle midzone, revealed the existence of two pathways that can initiate cleavage furrow ingression. One pathway depends on a well-organized spindle midzone and PLK1, while the other depends on Aurora B activity and centralspindlin at the equatorial cortex and can operate independently of PLK1. We further show that PLK1 inhibition sequesters centralspindlin onto the spindle midzone, making it unavailable for Aurora B at the equatorial cortex. We propose that PLK1 activity promotes the release of centralspindlin from the spindle midzone through inhibition of PRC1, allowing centralspindlin to function as a regulator of spindle midzone formation and as an activator of RhoA at the equatorial cortex.

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