scholarly journals Aurora B Phosphorylates Multiple Sites on Mitotic Centromere-associated Kinesin to Spatially and Temporally Regulate Its Function

2007 ◽  
Vol 18 (9) ◽  
pp. 3264-3276 ◽  
Author(s):  
Xin Zhang ◽  
Weijie Lan ◽  
Stephanie C. Ems-McClung ◽  
P. Todd Stukenberg ◽  
Claire E. Walczak
Keyword(s):  
Spindle Assembly ◽  
Aurora B ◽  
Phosphorylation Sites ◽  
Aurora B Kinase ◽  
Chromosome Congression ◽  
Chromosome Arm

Chromosome congression and segregation require the proper attachment of microtubules to the two sister kinetochores. Disruption of either Aurora B kinase or the Kinesin-13 mitotic centromere-associated kinesin (MCAK) increases chromosome misalignment and missegregation due to improper kinetochore–microtubule attachments. MCAK localization and activity are regulated by Aurora B, but how Aurora B phosphorylation of MCAK affects spindle assembly is unclear. Here, we show that the binding of MCAK to chromosome arms is also regulated by Aurora B and that Aurora B-dependent chromosome arm and centromere localization is regulated by distinct two-site phosphoregulatory mechanisms. MCAK association with chromosome arms is promoted by phosphorylation of T95 on MCAK, whereas phosphorylation of S196 on MCAK promotes dissociation from the arms. Although targeting of MCAK to centromeres requires phosphorylation of S110 on MCAK, dephosphorylation of T95 on MCAK increases the binding of MCAK to centromeres. Our study reveals a new role for Aurora B, which is to prevent excess MCAK binding to chromatin to facilitate chromatin-nucleated spindle assembly. Our study also shows that the interplay between multiple phosphorylation sites of MCAK may be critical to temporally and spatially control MCAK function.

scholarly journals Centromere-localized Aurora B kinase is required for the fidelity of chromosome segregation

2019 ◽  
Vol 219 (2) ◽  
Author(s):  
Cai Liang ◽  
Zhenlei Zhang ◽  
Qinfu Chen ◽  
Haiyan Yan ◽  
Miao Zhang ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Essential Role ◽  
Spindle Assembly Checkpoint ◽  
Histone H3 ◽  
Spindle Assembly ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Chromosome Missegregation ◽  
Proper Timing ◽  
Segregation Of Chromosomes

Aurora B kinase plays an essential role in chromosome bi-orientation, which is a prerequisite for equal segregation of chromosomes during mitosis. However, it remains largely unclear whether centromere-localized Aurora B is required for faithful chromosome segregation. Here we show that histone H3 Thr-3 phosphorylation (H3pT3) and H2A Thr-120 phosphorylation (H2ApT120) can independently recruit Aurora B. Disrupting H3pT3-mediated localization of Aurora B at the inner centromere impedes the decline in H2ApT120 during metaphase and causes H2ApT120-dependent accumulation of Aurora B at the kinetochore-proximal centromere. Consequently, silencing of the spindle assembly checkpoint (SAC) is delayed, whereas the fidelity of chromosome segregation is negligibly affected. Further eliminating an H2ApT120-dependent pool of Aurora B restores proper timing for SAC silencing but increases chromosome missegregation. Our data indicate that H2ApT120-mediated localization of Aurora B compensates for the loss of an H3pT3-dependent pool of Aurora B to correct improper kinetochore–microtubule attachments. This study provides important insights into how centromeric Aurora B regulates SAC and kinetochore attachment to microtubules to ensure error-free chromosome segregation.

scholarly journals Enrichment of Aurora B kinase at the inner kinetochore controls outer kinetochore assembly

2019 ◽  
Vol 218 (10) ◽  
pp. 3237-3257 ◽  
Author(s):  
Mary Kate Bonner ◽  
Julian Haase ◽  
Jason Swinderman ◽  
Hyunmi Halas ◽  
Lisa M. Miller Jenkins ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
Central Region ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Kinetochore Assembly ◽  
Egg Extracts ◽  
Chromosome Attachment

Outer kinetochore assembly enables chromosome attachment to microtubules and spindle assembly checkpoint (SAC) signaling in mitosis. Aurora B kinase controls kinetochore assembly by phosphorylating the Mis12 complex (Mis12C) subunit Dsn1. Current models propose Dsn1 phosphorylation relieves autoinhibition, allowing Mis12C binding to inner kinetochore component CENP-C. Using Xenopus laevis egg extracts and biochemical reconstitution, we found that autoinhibition of the Mis12C by Dsn1 impedes its phosphorylation by Aurora B. Our data indicate that the INCENP central region increases Dsn1 phosphorylation by enriching Aurora B at inner kinetochores, close to CENP-C. Furthermore, centromere-bound CENP-C does not exchange in mitosis, and CENP-C binding to the Mis12C dramatically increases Dsn1 phosphorylation by Aurora B. We propose that the coincidence of Aurora B and CENP-C at inner kinetochores ensures the fidelity of kinetochore assembly. We also found that the central region is required for the SAC beyond its role in kinetochore assembly, suggesting that kinetochore enrichment of Aurora B promotes the phosphorylation of other kinetochore substrates.

scholarly journals Spindle assembly and cytokinesis in the absence of chromosomes during Drosophila male meiosis

2003 ◽  
Vol 160 (7) ◽  
pp. 993-999 ◽  
Author(s):  
Elisabetta Bucciarelli ◽  
Maria Grazia Giansanti ◽  
Silvia Bonaccorsi ◽  
Maurizio Gatti
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly ◽  
Male Meiosis ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Spindle Formation ◽  
Central Spindle ◽  
Morphological Transformations ◽  
Bipolar Spindles ◽  
Drosophila Mutants

Alarge body of work indicates that chromosomes play a key role in the assembly of both acentrosomal and centrosome-containing spindles. In animal systems, the absence of chromosomes either prevents spindle formation or allows the assembly of a metaphase-like spindle that fails to evolve into an ana-telophase spindle. Here, we show that Drosophila secondary spermatocytes can assemble morphologically normal spindles in the absence of chromosomes. The Drosophila mutants fusolo and solofuso are severely defective in chromosome segregation and produce secondary spermatocytes that are devoid of chromosomes. The centrosomes of these anucleated cells form robust asters that give rise to bipolar spindles that undergo the same ana-telophase morphological transformations that characterize normal spindles. The cells containing chromosome-free spindles are also able to assemble regular cytokinetic structures and cleave normally. In addition, chromosome-free spindles normally accumulate the Aurora B kinase at their midzones. This suggests that the association of Aurora B with chromosomes is not a prerequisite for its accumulation at the central spindle, or for its function during cytokinesis.

scholarly journals Modeling the temporal evolution of the spindle assembly checkpoint and role of Aurora B kinase

2008 ◽  
Vol 105 (51) ◽  
pp. 20215-20220 ◽  
Author(s):  
H. B. Mistry ◽  
D. E. MacCallum ◽  
R. C. Jackson ◽  
M. A. J. Chaplain ◽  
F. A. Davidson
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Temporal Evolution ◽  
Spindle Assembly ◽  
Aurora B ◽  
Aurora B Kinase

scholarly journals Aurora B phosphorylates Bub1 to promote spindle assembly checkpoint signaling

2021 ◽  
Author(s):  
Babhrubahan Roy ◽  
Simon J. Y. Han ◽  
Adrienne N. Fontan ◽  
Ajit P. Joglekar
Keyword(s):  
Error Correction ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Mitotic Checkpoint ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Checkpoint Signaling ◽  
Binding Interface ◽  
Anaphase Onset ◽  
Error Correction Mechanism

SummaryAccurate chromosome segregation during cell division requires amphitelic attachment of each chromosome to the spindle apparatus. This is ensured by the Spindle Assembly Checkpoint (SAC) [1], which delays anaphase onset in response to unattached chromosomes, and an error correction mechanism, which eliminates syntelic chromosome attachments [2]. The SAC is activated by the Mps1 kinase. Mps1 sequentially phosphorylates the kinetochore protein Spc105/KNL1 to license the recruitment of several signaling proteins including Bub1. These proteins produce the Mitotic Checkpoint Complex (MCC), which delays anaphase onset [3-8]. The error correction mechanism is regulated by the Aurora B kinase, which phosphorylates the microtubule-binding interface of the kinetochore. Aurora B is also known to promote SAC signaling indirectly [9-12]. Here we present evidence that Aurora B kinase activity directly promotes MCC production in budding yeast and human cells. Using the ectopic SAC activation (eSAC) system, we find that the conditional dimerization of Aurora B (or an Aurora B recruitment domain) with either Bub1 or Mad1, but not the ‘MELT’ motifs in Spc105/KNL1, leads to a SAC-mediated mitotic arrest [13-16]. Importantly, ectopic MCC production driven by Aurora B requires the ability of Bub1 to bind both Mad1 and Cdc20. These and other data show that Aurora B cooperates with Bub1 to promote MCC production only after Mps1 licenses Bub1 recruitment to the kinetochore. This direct involvement of Aurora B in SAC signaling is likely important for syntelically attached sister kinetochores that must delay anaphase onset in spite of reduced Mps1 activity due to their end-on microtubule attachment.

scholarly journals Borealin directs recruitment of the CPC to oocyte chromosomes and movement to the microtubules

2021 ◽  
Vol 220 (6) ◽  
Author(s):  
Lin-Ing Wang ◽  
Tyler DeFosse ◽  
Janet K. Jang ◽  
Rachel A. Battaglia ◽  
Victoria F. Wagner ◽  
...  
Keyword(s):  
Homologous Chromosome ◽  
Spindle Assembly ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Central Spindle ◽  
Bipolar Spindle ◽  
Spindle Microtubules ◽  
Chromosome Passenger Complex

The chromosomes in the oocytes of many animals appear to promote bipolar spindle assembly. In Drosophila oocytes, spindle assembly requires the chromosome passenger complex (CPC), which consists of INCENP, Borealin, Survivin, and Aurora B. To determine what recruits the CPC to the chromosomes and its role in spindle assembly, we developed a strategy to manipulate the function and localization of INCENP, which is critical for recruiting the Aurora B kinase. We found that an interaction between Borealin and the chromatin is crucial for the recruitment of the CPC to the chromosomes and is sufficient to build kinetochores and recruit spindle microtubules. HP1 colocalizes with the CPC on the chromosomes and together they move to the spindle microtubules. We propose that the Borealin interaction with HP1 promotes the movement of the CPC from the chromosomes to the microtubules. In addition, within the central spindle, rather than at the centromeres, the CPC and HP1 are required for homologous chromosome bi-orientation.

scholarly journals Chromosome-directed oocyte spindle assembly depends HP1 and the Chromosomal Passenger Complex

2020 ◽  
Author(s):  
Lin-Ing Wang ◽  
Tyler DeFosse ◽  
Rachel A. Battaglia ◽  
Victoria F. Wagner ◽  
Kim S. McKim
Keyword(s):  
Homologous Chromosome ◽  
Spindle Assembly ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Chromosomal Passenger Complex ◽  
Central Spindle ◽  
Bipolar Spindle ◽  
Chromosomal Passenger ◽  
Spindle Microtubules

AbstractThe chromosomes in the oocytes of many animals appear to promote bipolar spindle assembly. In Drosophila oocytes, spindle assembly requires the chromosomal passenger complex (CPC), which consists of INCENP, Borealin, Survivin and Aurora B. To determine what recruits the CPC to the chromosomes and its role in spindle assembly, we developed a strategy to manipulate the function and localization of INCENP, which is critical for recruiting the Aurora B kinase. We found that an interaction between Borealin and HP1 is crucial for the initial recruitment of the CPC to the chromosomes and is sufficient to build kinetochores and recruit spindle microtubules. We also found that HP1 moves from the chromosomes to the spindle microtubules along with the CPC, and based on this, propose a mechanism for how the CPC moves from the chromosomes to the microtubules. Within the central spindle, rather than at the centromeres, the CPC and HP1 are required for homologous chromosome bi-orientation.

scholarly journals Sds22 regulates aurora B activity and microtubule–kinetochore interactions at mitosis

2010 ◽  
Vol 191 (1) ◽  
pp. 61-74 ◽  
Author(s):  
Markus Posch ◽  
Guennadi A. Khoudoli ◽  
Sam Swift ◽  
Emma M. King ◽  
Jennifer G. DeLuca ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Force Generation ◽  
Protein Phosphatase 1 ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Sister Kinetochore ◽  
Rate Of Recovery

We have studied Sds22, a conserved regulator of protein phosphatase 1 (PP1) activity, and determined its role in modulating the activity of aurora B kinase and kinetochore–microtubule interactions. Sds22 is required for proper progression through mitosis and localization of PP1 to mitotic kinetochores. Depletion of Sds22 increases aurora B T-loop phosphorylation and the rate of recovery from monastrol arrest. Phospho–aurora B accumulates at kinetochores in Sds22-depleted cells juxtaposed to critical kinetochore substrates. Sds22 modulates sister kinetochore distance and the interaction between Hec1 and the microtubule lattice and, thus, the activation of the spindle assembly checkpoint. These results demonstrate that Sds22 specifically defines PP1 function and localization in mitosis. Sds22 regulates PP1 targeting to the kinetochore, accumulation of phospho–aurora B, and force generation at the kinetochore–microtubule interface.

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