scholarly journals Balanced Activity of Three Mitotic Motors Is Required for Bipolar Spindle Assembly and Chromosome Segregation

Cell Reports ◽  
2014 ◽  
Vol 8 (4) ◽  
pp. 948-956 ◽  
Author(s):  
Roy G.H.P. van Heesbeen ◽  
Marvin E. Tanenbaum ◽  
René H. Medema
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly ◽  
Bipolar Spindle ◽  
Mitotic Motors

scholarly journals A microtubule polymerase cooperates with the kinesin-6 motor and a microtubule cross-linker to promote bipolar spindle assembly in the absence of kinesin-5 and kinesin-14 in fission yeast

2017 ◽  
Vol 28 (25) ◽  
pp. 3647-3659 ◽  
Author(s):  
Masashi Yukawa ◽  
Tomoki Kawakami ◽  
Masaki Okazaki ◽  
Kazunori Kume ◽  
Ngang Heok Tang ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Chromosome Segregation ◽  
Spindle Pole Body ◽  
Spindle Assembly ◽  
Spindle Pole ◽  
Temperature Sensitive ◽  
Bipolar Spindle ◽  
Pole Body ◽  
Cross Linker ◽  
Spindle Elongation

Accurate chromosome segregation relies on the bipolar mitotic spindle. In many eukaryotes, spindle formation is driven by the plus-end–directed motor kinesin-5 that generates outward force to establish spindle bipolarity. Its inhibition leads to the emergence of monopolar spindles with mitotic arrest. Intriguingly, simultaneous inactivation of the minus-end–directed motor kinesin-14 restores spindle bipolarity in many systems. Here we show that in fission yeast, three independent pathways contribute to spindle bipolarity in the absence of kinesin-5/Cut7 and kinesin-14/Pkl1. One is kinesin-6/Klp9 that engages with spindle elongation once short bipolar spindles assemble. Klp9 also ensures the medial positioning of anaphase spindles to prevent unequal chromosome segregation. Another is the Alp7/TACC-Alp14/TOG microtubule polymerase complex. Temperature-sensitive alp7cut7pkl1 mutants are arrested with either monopolar or very short spindles. Forced targeting of Alp14 to the spindle pole body is sufficient to render alp7cut7pkl1 triply deleted cells viable and promote spindle assembly, indicating that Alp14-mediated microtubule polymerization from the nuclear face of the spindle pole body could generate outward force in place of Cut7 during early mitosis. The third pathway involves the Ase1/PRC1 microtubule cross-linker that stabilizes antiparallel microtubules. Our study, therefore, unveils multifaceted interplay among kinesin-dependent and -independent pathways leading to mitotic bipolar spindle assembly.

Aurora/Ipl1p-related kinases, a new oncogenic family of mitotic serine-threonine kinases

1999 ◽  
Vol 112 (21) ◽  
pp. 3591-3601 ◽  
Author(s):  
R. Giet ◽  
C. Prigent
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drosophila Melanogaster ◽  
Chromosome Segregation ◽  
Mammalian Cells ◽  
Spindle Assembly ◽  
Mitotic Apparatus ◽  
Bipolar Spindle ◽  
The Past ◽  
Centrosome Separation ◽  
Threonine Kinases

During the past five years, a growing number of serine-threonine kinases highly homologous to the Saccharomyces cerevisiae Ipl1p kinase have been isolated in various organisms. A Drosophila melanogaster homologue, aurora, was the first to be isolated from a multicellular organism. Since then, several related kinases have been found in mammalian cells. They localise to the mitotic apparatus: in the centrosome, at the poles of the bipolar spindle or in the midbody. The kinases are necessary for completion of mitotic events such as centrosome separation, bipolar spindle assembly and chromosome segregation. Extensive research is now focusing on these proteins because the three human homologues are overexpressed in various primary cancers. Furthermore, overexpression of one of these kinases transforms cells. Because of the myriad of kinases identified, we suggest a generic name: Aurora/Ipl1p-related kinase (AIRK). We denote AIRKs with a species prefix and a number, e.g. HsAIRK1.

scholarly journals OsMTOPVIB is required for meiotic bipolar spindle assembly

2019 ◽  
Vol 116 (32) ◽  
pp. 15967-15972 ◽  
Author(s):  
Zhihui Xue ◽  
Changzhen Liu ◽  
Wenqing Shi ◽  
Yongjie Miao ◽  
Yi Shen ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Chromosome Segregation ◽  
Spindle Assembly ◽  
Strand Break ◽  
Microtubule Assembly ◽  
Multipolar Spindle ◽  
Bipolar Spindle ◽  
Multipolar Spindles ◽  
Bipolar Spindles ◽  
Plant Meiosis

The organization of microtubules into a bipolar spindle is essential for chromosome segregation. Both centrosome and chromatin-dependent spindle assembly mechanisms are well studied in mouse, Drosophila melanogaster, and Xenopus oocytes; however, the mechanism of bipolar spindle assembly in plant meiosis remains elusive. According to our observations of microtubule assembly in Oryza sativa, Zea mays, Arabidopsis thaliana, and Solanum lycopersicum, we propose that a key step of plant bipolar spindle assembly is the correction of the multipolar spindle into a bipolar spindle at metaphase I. The multipolar spindles failed to transition into bipolar ones in OsmtopVIB with the defect in double-strand break (DSB) formation. However, bipolar spindles were normally assembled in several other mutants lacking DSB formation, such as Osspo11-1, pair2, and crc1, indicating that bipolar spindle assembly is independent of DSB formation. We further revealed that the mono-orientation of sister kinetochores was prevalent in OsmtopVIB, whereas biorientation of sister kinetochores was frequently observed in Osspo11-1, pair2, and crc1. In addition, mutations of the cohesion subunit OsREC8 resulted in biorientation of sister kinetochores as well as bipolar spindles even in the background of OsmtopVIB. Therefore, we propose that biorientation of the kinetochore is required for bipolar spindle assembly in the absence of homologous recombination.

scholarly journals A Kinesin Mutant with an Atypical Bipolar Spindle Undergoes Normal Mitosis

2003 ◽  
Vol 14 (4) ◽  
pp. 1717-1726 ◽  
Author(s):  
A. I. Marcus ◽  
W. Li ◽  
H. Ma ◽  
R. J. Cyr
Keyword(s):  
Chromosome Segregation ◽  
Plant Cells ◽  
Spindle Assembly ◽  
Wild Type Allele ◽  
Wild Type ◽  
Bipolar Spindle ◽  
Type Allele ◽  
Spindle Poles ◽  
Normal Mitosis ◽  
Arabidopsis Cells

Motor proteins have been implicated in various aspects of mitosis, including spindle assembly and chromosome segregation. Here, we show that acentrosomal Arabidopsis cells that are mutant for the kinesin, ATK1, lack microtubule accumulation at the predicted spindle poles during prophase and have reduced spindle bipolarity during prometaphase. Nonetheless, all abnormalities are rectified by anaphase and chromosome segregation appears normal. We conclude that ATK1 is required for normal microtubule accumulation at the spindle poles during prophase and possibly functions in spindle assembly during prometaphase. Because aberrant spindle morphology in these mutants is resolved by anaphase, we postulate that mitotic plant cells contain an error-correcting mechanism. Moreover, ATK1 function seems to be dosage-dependent, because cells containing one wild-type allele take significantly longer to proceed to anaphase as compared with cells containing two wild-type alleles.

scholarly journals Mechanosensitive nuclear asymmetries define a bipolar spindle scaffold to ensure mitotic fidelity

2019 ◽  
Author(s):  
Vanessa Nunes ◽  
Margarida Dantas ◽  
Domingos Castro ◽  
Elisa Vitiello ◽  
Irène Wang ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Molecular Motors ◽  
Mitotic Chromosome ◽  
Spindle Assembly ◽  
Division Plane ◽  
Bipolar Spindle ◽  
Prophase Nucleus ◽  
Cytoskeletal Networks ◽  
Mitotic Chromosome Condensation ◽  
Division Plane Orientation

AbstractDuring prophase, centrosomes need to separate and position to correctly assemble the mitotic spindle. This process occurs through the action of molecular motors, cytoskeletal networks and the nucleus. How the combined activity of these different components is spatiotemporally regulated to ensure efficient spindle assembly remains unclear. Here we show that during prophase the centrosomes-nucleus axis reorients, so that centrosomes are positioned on the shortest nuclear axis at nuclear envelope (NE) breakdown. This centrosomes-nucleus configuration depends on mechanical cues generated by mitotic chromosome condensation on the prophase nucleus. We further show these mechanosensitive cues act through SUN1/2 and NudE+NudEL to enable the polarized loading of Dynein on the NE. Finally, we observe this centrosome configuration favors the establishment of an initial bipolar spindle scaffold, facilitating chromosome capture and accurate segregation, without compromising division plane orientation. We propose that chromosome segregation fidelity depends on the mechanical properties of the prophase nucleus that facilitate spindle assembly by regulating NE-Dynein localization.

scholarly journals Nek2-mediated GAS2L1 phosphorylation and centrosome-linker disassembly induce centrosome disjunction

2020 ◽  
Vol 219 (5) ◽  
Author(s):  
Franco K.C. Au ◽  
Bill K.T. Hau ◽  
Robert Z. Qi
Keyword(s):  
Chromosome Segregation ◽  
Binding Protein ◽  
Spindle Assembly ◽  
Actin Binding ◽  
Spindle Formation ◽  
Bipolar Spindle ◽  
Actin Binding Protein ◽  
Calponin Homology

Centrosome disjunction occurs in late G2 to facilitate bipolar spindle formation and is mediated by the NIMA-related kinase Nek2. Here, we show that GAS2L1, a microtubule- and F-actin–binding protein required for centrosome disjunction, undergoes Nek2-mediated phosphorylation at Ser352 in G2/M. The phosphorylation is essential for centrosome disjunction in late G2 and for proper spindle assembly and faithful chromosome segregation in mitosis. GAS2L1 contains a calponin-homology (CH) domain and a GAS2-related (GAR) domain, which bind to F-actin and microtubules, respectively. Notably, the CH and GAR domains bind to each other to inhibit the functions of both domains, and Ser352 phosphorylation disrupts the interaction between the two domains and relieves the autoinhibition. We dissected the roles of the GAS2L1 phosphorylation and of centrosome-linker disassembly, which is another Nek2-mediated event, and found that these events together trigger centrosome disjunction. Therefore, our findings demonstrate the concerted Nek2 actions that split the centrosomes in late G2.

scholarly journals The impact of chromosomes and centrosomes on spindle assembly as observed in living cells.

1995 ◽  
Vol 129 (5) ◽  
pp. 1287-1300 ◽  
Author(s):  
D Zhang ◽  
R B Nicklas
Keyword(s):  
Spindle Assembly ◽  
Living Cells ◽  
Microtubule Dynamics ◽  
Specific Site ◽  
Polarization Microscopy ◽  
Spindle Microtubule ◽  
Single Chromosome ◽  
Bipolar Spindle ◽  
The Impact

We analyzed the role that chromosomes, kinetochores, and centrosomes play in spindle assembly in living grasshopper spermatocytes by reconstructing spindles lacking certain components. We used video-enhanced, polarization microscopy to distinguish the effect of each component on spindle microtubule dynamics and we discovered that both chromosomes and centrosomes make potent and very different contributions to the organization of the spindle. Remarkably, the position of a single chromosome can markedly affect the distribution of microtubules within a spindle or even alter the fate of spindle assembly. In an experimentally constructed spindle having only one chromosome, moving the chromosome to one of the two poles induces a dramatic assembly of microtubules at the nearer pole and a concomitant disassembly at the farther pole. So long as a spindle carries a single chromosome it will persist normally. A spindle will also persist even when all chromosomes are detached and then removed from the cell. If, however, a single chromosome remains in the cell but is detached from the spindle and kept in the cytoplasm, the spindle disassembles. One might expect the effect of chromosomes on spindle assembly to relate to a property of a specific site on each chromosome, perhaps the kinetochore. We have ruled out that possibility by showing that it is the size of chromosomes rather than the number of kinetochores that matters. Although chromosomes affect spindle assembly, they cannot organize a spindle in the absence of centrosomes. In contrast, centrosomes can organize a functional bipolar spindle in the absence of chromosomes. If both centrosomes and chromosomes are removed from the cell, the spindle quickly disappears.

scholarly journals A role for I B kinase 2 in bipolar spindle assembly

2007 ◽  
Vol 104 (43) ◽  
pp. 16940-16945 ◽  
Author(s):  
J. T. Irelan ◽  
T. J. Murphy ◽  
P. D. DeJesus ◽  
H. Teo ◽  
D. Xu ◽  
...  
Keyword(s):  
Spindle Assembly ◽  
Bipolar Spindle

scholarly journals Monitoring the fidelity of mitotic chromosome segregation by the spindle assembly checkpoint

2011 ◽  
Vol 44 (5) ◽  
pp. 391-400 ◽  
Author(s):  
P. Silva ◽  
J. Barbosa ◽  
A. V. Nascimento ◽  
J. Faria ◽  
R. Reis ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Mitotic Chromosome ◽  
Spindle Assembly
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