scholarly journals Stu1 inversely regulates kinetochore capture and spindle stability

2009 ◽  
Vol 23 (23) ◽  
pp. 2778-2791 ◽  
Author(s):  
J. Ortiz ◽  
C. Funk ◽  
A. Schafer ◽  
J. Lechner
Keyword(s):  
Spindle Stability

The mitosis-regulating and protein-protein interaction activities of Astrin are controlled by Aurora-A-induced phosphorylation

2014 ◽  
Vol 307 (5) ◽  
pp. C466-C478 ◽  
Author(s):  
Shao-Chih Chiu ◽  
Jo-Mei Maureen Chen ◽  
Tong-You Wade Wei ◽  
Tai-Shan Cheng ◽  
Ya-Hui Candice Wang ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Spindle Assembly Checkpoint ◽  
Morphological Changes ◽  
Spindle Assembly ◽  
Aurora A ◽  
Protein Protein Interaction ◽  
Daughter Cells ◽  
Sister Chromatids ◽  
Complicated Process ◽  
Spindle Stability

Cells display dramatic morphological changes in mitosis, where numerous factors form regulatory networks to orchestrate the complicated process, resulting in extreme fidelity of the segregation of duplicated chromosomes into two daughter cells. Astrin regulates several aspects of mitosis, such as maintaining the cohesion of sister chromatids by inactivating Separase and stabilizing spindle, aligning and segregating chromosomes, and silencing spindle assembly checkpoint by interacting with Src kinase-associated phosphoprotein (SKAP) and cytoplasmic linker-associated protein-1α (CLASP-1α). To understand how Astrin is regulated in mitosis, we report here that Astrin acts as a mitotic phosphoprotein, and Aurora-A phosphorylates Astrin at Ser115. The phosphorylation-deficient mutant Astrin S115A abnormally activates spindle assembly checkpoint and delays mitosis progression, decreases spindle stability, and induces chromosome misalignment. Mechanistic analyses reveal that Astrin phosphorylation mimicking mutant S115D, instead of S115A, binds and induces ubiquitination and degradation of securin, which sequentially activates Separase, an enzyme required for the separation of sister chromatids. Moreover, S115A fails to bind mitosis regulators, including SKAP and CLASP-1α, which results in the mitotic defects observed in Astrin S115A-transfected cells. In conclusion, Aurora-A phosphorylates Astrin and guides the binding of Astrin to its cellular partners, which ensures proper progression of mitosis.

scholarly journals Klp2 and Ase1 synergize to maintain meiotic spindle stability during metaphase I

2020 ◽  
Author(s):  
Fan Zheng ◽  
Fenfen Dong ◽  
Shuo Yu ◽  
Tianpeng Li ◽  
Yanze Jian ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Yeast Cells ◽  
Meiotic Spindle ◽  
Homologous Chromosomes ◽  
Spindle Dynamics ◽  
Live Cell Microscopy ◽  
Spindle Stability ◽  
Cell Microscopy ◽  
Mitosis And Meiosis ◽  
Meiosis I

ABSTRACTThe spindle apparatus segregates bi-oriented sister chromatids during mitosis but mono-oriented homologous chromosomes during meiosis I. It has remained unclear if similar molecular mechanisms operate to regulate spindle dynamics during mitosis and meiosis I. Here, we employed live-cell microscopy to compare the spindle dynamics of mitosis and meiosis I in fission yeast cells and demonstrated that the conserved kinesin-14 motor Klp2 plays a specific role in maintaining metaphase spindle length during meiosis I, but not during mitosis. Moreover, the maintenance of metaphase spindle stability during meiosis I requires the synergism between Klp2 and the conserved microtubule crosslinker Ase1 as the absence of both proteins causes exacerbated defects in metaphase spindle stability. The synergism is not necessary for regulating mitotic spindle dynamics. Hence, our work reveals a new molecular mechanism underlying meiotic spindle dynamics and provides insights into understanding differential regulation of meiotic and mitotic events.

scholarly journals Contractile Ring-independent Localization of DdINCENP, a Protein Important for Spindle Stability and Cytokinesis

2006 ◽  
Vol 17 (2) ◽  
pp. 779-788 ◽  
Author(s):  
Qian Chen ◽  
Hui Li ◽  
Arturo De Lozanne
Keyword(s):  
Myosin Ii ◽  
Cleavage Furrow ◽  
Contractile Ring ◽  
Subsequent Formation ◽  
Daughter Cells ◽  
Chromosomal Passenger ◽  
Spindle Midzone ◽  
Spindle Stability ◽  
Passenger Protein

Dictyostelium DdINCENP is a chromosomal passenger protein associated with centromeres, the spindle midzone, and poles during mitosis and the cleavage furrow during cytokinesis. Disruption of the single DdINCENP gene revealed important roles for this protein in mitosis and cytokinesis. DdINCENP null cells lack a robust spindle midzone and are hypersensitive to microtubule-depolymerizing drugs, suggesting that their spindles may not be stable. Furthermore DdCP224, a protein homologous to the microtubule-stabilizing protein TOGp/XMAP215, was absent from the spindle midzone of DdINCENP null cells. Overexpression of DdCP224 rescued the weak spindle midzone defect of DdINCENP null cells. Although not required for the localization of the myosin II contractile ring and subsequent formation of a cleavage furrow, DdINCENP is important for the abscission of daughter cells at the end of cytokinesis. Finally, we show that the localization of DdINCENP at the cleavage furrow is modulated by myosin II but it occurs by a mechanism different from that controlling the formation of the contractile ring.

scholarly journals Clathrin’s adaptor interaction sites are repurposed to stabilize microtubules during mitosis

2019 ◽  
Author(s):  
Arnaud Rondelet ◽  
Yu-Chih Lin ◽  
Divya Singh ◽  
Arthur T. Porfetye ◽  
Harish C. Thakur ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Interaction Mechanism ◽  
Adaptor Proteins ◽  
Interaction Sites ◽  
Microtubule Attachment ◽  
Chromosome Congression ◽  
Chromosome Alignment ◽  
Clathrin Adaptor ◽  
Spindle Stability ◽  
First Time

SUMMARYClathrin plays an important role to ensure mitotic spindle stability and efficient chromosome alignment, independently of its well-characterized functions in vesicle trafficking. While clathrin clearly localizes to the mitotic spindle and kinetochore-fiber microtubule bundles, the mechanisms by which clathrin stabilizes microtubules have remained elusive. Here we show that clathrin adaptor interaction sites on clathrin heavy chain (CHC) are repurposed during mitosis to directly recruit the microtubule-stabilizing protein GTSE1 to the mitotic spindle. Structural analyses reveal that multiple clathrin-box motifs on GTSE1 interact directly with different clathrin adaptor interaction sites on CHC, in a manner structurally analogous to that which occurs between adaptor proteins and CHC near membranes. Specific disruption of this interaction in cells releases GTSE1 from spindles and causes defects in chromosome alignment. Surprisingly, this disruption causes destabilization of astral microtubules, but not kinetochore-microtubule attachments, and the resulting chromosome alignment defect is due to a failure of chromosome congression independent of kinetochore-microtubule attachment stability. Finally, we show that GTSE1 recruited to the spindle by clathrin stabilizes microtubules and promotes chromosome congression by inhibiting the activity of the microtubule depolymerase MCAK. This work thus uncovers a novel role of clathrin to stabilize non-kinetochore-fiber microtubules to support chromosome congression. This role is carried out via clathrin adaptor-type interactions of CHC with GTSE1, defining for the first time an important repurposing of this endocytic interaction mechanism during mitosis.

scholarly journals TPX2 Amplification-Driven Aberrant Mitosis in Long-Term Cultured Human Embryonic Stem Cells

2021 ◽  
Author(s):  
Ho-Chang Jeong ◽  
Young-Hyun Go ◽  
Joong-Gon Shin ◽  
Yun-Jeong Kim ◽  
Min-Guk Cho ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mitotic Progression ◽  
Genome Wide ◽  
Hesc Culture ◽  
Spindle Stability

AbstractAlthough human embryonic stem cells (hESCs) are equipped with highly effective machinery for the maintenance of genome integrity, the frequency of genetic aberrations during long-term in vitro hESC culture has been a serious issue that raises concerns over their safety in future clinical applications. By passaging hESCs over a broad range of timepoints, we found that mitotic aberrations, such as the delay of mitosis, multipolar centrosomes, and chromosome mis-segregation, were increased in the late-passaged hESCs (LP-hESCs) in parallel with polyploidy compared to early-passaged hESCs (EP-hESCs). Through high-resolution genome-wide approaches and by following transcriptome analysis, we found that LP-hESCs with a minimal amplicon in chromosome 20q11.21 highly expressed TPX2 (targeting protein for Xklp2), a key protein for governing spindle assembly and cancer malignancy. Consistent with these findings, the inducible expression of TPX2 in EP-hESCs reproduced aberrant mitotic events, such as the delay of mitotic progression, spindle stability, misaligned chromosomes, and polyploidy. This data suggests that the amplification and increased transcription of the TPX2 gene at 20q11.21 could contribute to an increase in aberrant mitosis due to altered spindle dynamics.

scholarly journals The nucleolar RNA methyltransferase Misu (NSun2) is required for mitotic spindle stability

2009 ◽  
Vol 186 (1) ◽  
pp. 27-40 ◽  
Author(s):  
Shobbir Hussain ◽  
Sandra Blanco Benavente ◽  
Elisabete Nascimento ◽  
Ilaria Dragoni ◽  
Agata Kurowski ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Multipolar Spindles ◽  
Direct Target Gene ◽  
Dividing Cells ◽  
Direct Target ◽  
Spindle Stability ◽  
Sun Domain ◽  
Nucleolar Rna

Myc-induced SUN domain–containing protein (Misu or NSun2) is a nucleolar RNA methyltransferase important for c-Myc–induced proliferation in skin, but the mechanisms by which Misu contributes to cell cycle progression are unknown. In this study, we demonstrate that Misu translocates from the nucleoli in interphase to the spindle in mitosis as an RNA–protein complex that includes 18S ribosomal RNA. Functionally, depletion of Misu caused multiple mitotic defects, including formation of unstructured spindles, multipolar spindles, and chromosome missegregation, leading to aneuploidy and cell death. The presence of both RNA and Misu is required for correct spindle assembly, and this process is independent of active translation. Misu might mediate its function at the spindle by recruiting nucleolar and spindle-associated protein (NuSAP), an essential microtubule-stabilizing and bundling protein. We further identify NuSAP as a novel direct target gene of c-Myc. Collectively, our results suggest a novel mechanism by which c-Myc promotes proliferation by stabilizing the mitotic spindle in fast-dividing cells via Misu and NuSAP.

scholarly journals Chromosome passenger complexes control anaphase duration and spindle elongation via a kinesin-5 brake

2011 ◽  
Vol 193 (2) ◽  
pp. 285-294 ◽  
Author(s):  
Daniel K. Rozelle ◽  
Scott D. Hansen ◽  
Kenneth B. Kaplan
Keyword(s):  
Chromosome Segregation ◽  
Budding Yeast ◽  
Mitotic Exit ◽  
Mitotic Exit Network ◽  
Spindle Midzone ◽  
Spindle Elongation ◽  
Spindle Stability

During mitosis, chromosome passenger complexes (CPCs) exhibit a well-conserved association with the anaphase spindle and have been implicated in spindle stability. However, their precise effect on the spindle is not clear. In this paper, we show, in budding yeast, that a CPC consisting of CBF3, Bir1, and Sli15, but not Ipl1, is required for normal spindle elongation. CPC mutants slow spindle elongation through the action of the bipolar kinesins Cin8 and Kip1. The same CPC mutants that slow spindle elongation also result in the enrichment of Cin8 and Kip1 at the spindle midzone. Together, these findings argue that CPCs function to organize the spindle midzone and potentially switch motors between force generators and molecular brakes. We also find that slowing spindle elongation delays the mitotic exit network (MEN)–dependent release of Cdc14, thus delaying spindle breakdown until a minimal spindle size is reached. We propose that these CPC- and MEN-dependent mechanisms are important for coordinating chromosome segregation with spindle breakdown and mitotic exit.

scholarly journals Meiotic spindle stability depends on MAPK-interacting and spindle-stabilizing protein (MISS), a new MAPK substrate

2002 ◽  
Vol 157 (4) ◽  
pp. 603-613 ◽  
Author(s):  
Christophe Lefebvre ◽  
M. Emilie Terret ◽  
Alexandre Djiane ◽  
Pascale Rassinier ◽  
Bernard Maro ◽  
...  
Keyword(s):  
Antisense Rna ◽  
Mapk Pathway ◽  
Meiotic Spindle ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein ◽  
Cytostatic Factor ◽  
Morpholino Oligonucleotides ◽  
Spindle Stability ◽  
Two Hybrid ◽  
Segregation Of Chromosomes

Vertebrate oocytes arrest in the second metaphase of meiosis (metaphase II [MII]) by an activity called cytostatic factor (CSF), with aligned chromosomes and stable spindles. Segregation of chromosomes occurs after fertilization. The Mos/…/MAPK (mitogen-activated protein kinases) pathway mediates this MII arrest. Using a two-hybrid screen, we identified a new MAPK partner from a mouse oocyte cDNA library. This protein is unstable during the first meiotic division and accumulates only in MII, where it localizes to the spindle. It is a substrate of the Mos/…/MAPK pathway. The depletion of endogenous RNA coding for this protein by three different means (antisense RNA, double-stranded [ds] RNA, or morpholino oligonucleotides) induces severe spindle defects specific to MII oocytes. Overexpressing the protein from an RNA not targeted by the morpholino rescues spindle destabilization. However, dsRNA has no effect on the first two mitotic divisions. We therefore have discovered a new MAPK substrate involved in maintaining spindle integrity during the CSF arrest of mouse oocytes, called MISS (for MAP kinase–interacting and spindle-stabilizing protein).

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