scholarly journals Mutual Dependence of Mob1 and the Chromosomal Passenger Complex for Localization during Mitosis

2010 ◽  
Vol 21 (3) ◽  
pp. 380-392 ◽  
Author(s):  
Lori Jo Wilmeth ◽  
Sanjay Shrestha ◽  
Gilbert Montaño ◽  
Jennifer Rashe ◽  
Charles Bradley Shuster
Keyword(s):  
Mitotic Exit ◽  
Signaling Cascades ◽  
Mitotic Progression ◽  
Chromosomal Passenger Complex ◽  
Related Family ◽  
Cytoplasmic Material ◽  
Spindle Poles ◽  
Chromosomal Passenger ◽  
Early Anaphase ◽  
Spindle Midzone

The spatial and temporal coordination of chromosome segregation with cytokinesis is essential to ensure that each daughter cell receives the correct complement of chromosomal and cytoplasmic material. In yeast, mitotic exit and cytokinesis are coordinated by signaling cascades whose terminal components include a nuclear Dbf2-related family kinase and a noncatalytic subunit, Mps one binding (Mob) 1. There are five human Mob1 isoforms, all of which display redundant localization patterns at the spindle poles and kinetochores in early mitosis, and the spindle midzone during cytokinesis. Mob1 shares similar localization patterns to Polo-like kinase (Plk1) and the chromosomal passenger complex (CPC), and although depletion of Plk1 resulted in a loss of Mob1 from the spindle poles, Mob1 recruitment to kinetochores was unaffected. Conversely, disruption of CPC signaling resulted in a loss of Mob1 from kinetochores without disrupting recruitment to the spindle poles. In Mob1-depleted cells, the relocalization of the CPC and mitotic kinesin-like protein (MKLP) 2 to the spindle midzone was delayed during early anaphase, and as a consequence, the midzone recruitment of MKLP1 also was affected. Together, these results suggest that Mob1 and the other mammalian orthologues of the mitotic exit network regulate mitotic progression by facilitating the timely mobilization of the CPC to the spindle midzone.

scholarly journals Liquid-liquid phase separation of the chromosomal passenger complex drives parallel bundling of midzone microtubules

2022 ◽  
Author(s):  
Ewa Niedzialkowska ◽  
Tan M Truong ◽  
Luke A Eldredge ◽  
Stefanie Redemann ◽  
Denis Chretien ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Chromosome Segregation ◽  
Dynamic Structure ◽  
Liquid Phase Separation ◽  
Chromosomal Passenger Complex ◽  
Chromosomal Passenger ◽  
Spindle Midzone ◽  
Liquid Liquid Phase Separation

The spindle midzone is a dynamic structure that forms during anaphase, mediates chromosome segregation, and provides a signaling platform to position the cleavage furrow. The spindle midzone comprises two antiparallel bundles of microtubules (MTs) but the process of their formation is poorly understood. Here, we show that the Chromosomal Passenger Complex (CPC) undergoes liquid-liquid phase separation (LLPS) to generate parallel MT bundles in vitro when incubated with free tubulin and GTP. MT bundles emerge from CPC droplets with protruding minus-ends that then grow into long, tapered MT structures. During this growth, the CPC in condensates apparently reorganize to coat and bundle the resulting MT structures. CPC mutants attenuated for LLPS or MT binding prevented the generation of parallel MT bundles in vitro and reduced the number of MTs present at spindle midzones in HeLa cells. Our data uncovers a kinase-independent function of the CPC and provides models for how cells generate parallel-bundled MT structures that are important for the assembly of the mitotic spindle.

scholarly journals The chromosomal passenger complex and centralspindlin independently contribute to contractile ring assembly

2011 ◽  
Vol 193 (1) ◽  
pp. 155-169 ◽  
Author(s):  
Lindsay Lewellyn ◽  
Ana Carvalho ◽  
Arshad Desai ◽  
Amy S. Maddox ◽  
Karen Oegema
Keyword(s):  
Contractile Ring ◽  
Chromosomal Passenger Complex ◽  
Ring Assembly ◽  
Assembly Pathway ◽  
Chromosomal Passenger ◽  
Spindle Midzone ◽  
Ring Constriction ◽  
Simultaneous Inhibition ◽  
Control Transformation ◽  
Equatorial Band

The chromosomal passenger complex (CPC) and centralspindlin are conserved cytokinesis regulators that localize to the spindle midzone, which forms between the separating chromosomes. Previous work placed the CPC and centralspindlin in a linear pathway that governs midzone formation. Using Caenorhabditis elegans embryos, we test whether there is a similar linear relationship between centralspindlin and the CPC in contractile ring constriction during cytokinesis. We show that simultaneous inhibition of the CPC kinase Aurora BAIR-2 and the centralspindlin component MKLP1ZEN-4 causes an additive constriction defect. Consistent with distinct roles for the proteins, inhibition of filamentous septin guanosine triphosphatases alleviates constriction defects in Aurora BAIR-2–inhibited embryos, whereas inhibition of Rac does so in MKLP1ZEN-4-inhibited embryos. Centralspindlin and the CPC are not required to enrich ring proteins at the cell equator but instead regulate formation of a compact mature ring. Therefore, in contrast to the linear midzone assembly pathway, centralspindlin and the CPC make independent contributions to control transformation of the sheet-like equatorial band into a ribbon-like contractile ring at the furrow tip.

scholarly journals Kinesins relocalize the chromosomal passenger complex to the midzone for spindle disassembly

2018 ◽  
Vol 217 (5) ◽  
pp. 1687-1700 ◽  
Author(s):  
Itziar Ibarlucea-Benitez ◽  
Luke S. Ferro ◽  
David G. Drubin ◽  
Georjana Barnes
Keyword(s):  
Single Molecule ◽  
Molecular Mechanisms ◽  
Chromosomal Passenger Complex ◽  
Late Anaphase ◽  
Chromosomal Passenger ◽  
Spindle Disassembly ◽  
Spindle Midzone ◽  
Chromosome Separation

Mitotic spindle disassembly after chromosome separation is as important as spindle assembly, yet the molecular mechanisms for spindle disassembly are unclear. In this study, we investigated how the chromosomal passenger complex (CPC), which contains the Aurora B kinase Ipl1, swiftly concentrates at the spindle midzone in late anaphase, and we researched the role of this dramatic relocalization during spindle disassembly. We showed that the kinesins Kip1 and Kip3 are essential for CPC relocalization. In cells lacking Kip1 and Kip3, spindle disassembly is severely delayed until after contraction of the cytokinetic ring. Purified Kip1 and Kip3 interact directly with the CPC and recruit it to microtubules in vitro, and single-molecule experiments showed that the CPC diffuses dynamically on microtubules but that diffusion stops when the CPC encounters a Kip1 molecule. We propose that Kip1 and Kip3 trap the CPC at the spindle midzone in late anaphase to ensure timely spindle disassembly.

scholarly journals Two mechanisms coordinate the recruitment of the chromosomal passenger complex to the plane of cell division

2017 ◽  
Vol 28 (25) ◽  
pp. 3634-3646 ◽  
Author(s):  
Jennifer Landino ◽  
Stephen R. Norris ◽  
Muyi Li ◽  
Edward R. Ballister ◽  
Michael A. Lampson ◽  
...  
Keyword(s):  
Live Cell Imaging ◽  
Cell Imaging ◽  
Cleavage Plane ◽  
Mitotic Exit ◽  
Actin Binding ◽  
Alternative Mechanism ◽  
Dependent Manner ◽  
Chromosomal Passenger Complex ◽  
Division Plane ◽  
Chromosomal Passenger

During cytokinesis, the chromosomal passenger complex (CPC) promotes midzone organization, specifies the cleavage plane, and regulates furrow contractility. The localizations of the CPC are coupled to its cytokinetic functions. At the metaphase-to-anaphase transition, the CPC dissociates from centromeres and localizes to midzone microtubules and the equatorial cortex. CPC relocalization to the cell middle is thought to depend on MKlp2-driven, plus end–directed transport. In support of this idea, MKlp2 depletion impairs cytokinesis; however, cytokinesis failure stems from furrow regression rather than failed initiation of furrowing. This suggests that an alternative mechanism(s) may concentrate the CPC at the division plane. We show here that direct actin binding, via the inner centromere protein (INCENP), enhances CPC enrichment at the equatorial cortex, thus acting in tandem with MKlp2. INCENP overexpression rescues furrowing in MKlp2-depleted cells in an INCENP-actin binding–dependent manner. Using live-cell imaging, we also find that MKlp2-dependent targeting of the CPC is biphasic. MKlp2 targets the CPC to the anti-parallel microtubule overlap of the midzone, after which the MKlp2-CPC complex moves in a nondirected manner. Collectively, our work suggests that both actin binding and MKlp2-dependent midzone targeting cooperate to precisely position the CPC during mitotic exit, and that these pathways converge to ensure successful cleavage furrow ingression.

scholarly journals The Cul3–KLHL21 E3 ubiquitin ligase targets Aurora B to midzone microtubules in anaphase and is required for cytokinesis

2009 ◽  
Vol 187 (6) ◽  
pp. 791-800 ◽  
Author(s):  
Sarah Maerki ◽  
Michael H. Olma ◽  
Titu Staubli ◽  
Patrick Steigemann ◽  
Daniel W. Gerlich ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Ubiquitin Ligases ◽  
Aurora B ◽  
Chromosomal Passenger Complex ◽  
Chromosome Alignment ◽  
Chromosomal Passenger ◽  
Spindle Midzone ◽  
Broad Complex

Cul3 (Cullin3)-based E3 ubiquitin ligases recently emerged as critical regulators of mitosis. In this study, we identify two mammalian BTB (Bric-a-brac–Tramtrack–Broad complex)-Kelch proteins, KLHL21 and KLHL22, that interact with Cul3 and are required for efficient chromosome alignment. Interestingly, KLHL21 but not KLHL22 is necessary for cytokinesis and regulates translocation of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase, similar to the previously described BTB-Kelch proteins KLHL9 and KLHL13. KLHL21 directly binds to Aurora B and mediates ubiquitination of Aurora B in vitro. In contrast to KLHL9 and KLHL13, KLHL21 localizes to midzone microtubules in anaphase and recruits Aurora B and Cul3 to this region. Together, our results suggest that different Cul3 adaptors nonredundantly regulate Aurora B during mitosis, possibly by ubiquitinating different pools of Aurora B at distinct subcellular localizations.

scholarly journals Borealin

2004 ◽  
Vol 166 (2) ◽  
pp. 179-191 ◽  
Author(s):  
Reto Gassmann ◽  
Ana Carvalho ◽  
Alexander J. Henzing ◽  
Sandrine Ruchaud ◽  
Damien F. Hudson ◽  
...  
Keyword(s):  
Rna Interference ◽  
Histone H3 ◽  
Aurora B ◽  
Mitotic Progression ◽  
Aurora B Kinase ◽  
Chromosomal Passenger Complex ◽  
Central Spindle ◽  
Chromosomal Passenger ◽  
Bipolar Spindles

The chromosomal passenger complex of Aurora B kinase, INCENP, and Survivin has essential regulatory roles at centromeres and the central spindle in mitosis. Here, we describe Borealin, a novel member of the complex. Approximately half of Aurora B in mitotic cells is complexed with INCENP, Borealin, and Survivin; and Borealin binds Survivin and INCENP in vitro. A second complex contains Aurora B and INCENP, but no Borealin or Survivin. Depletion of Borealin by RNA interference delays mitotic progression and results in kinetochore–spindle misattachments and an increase in bipolar spindles associated with ectopic asters. The extra poles, which apparently form after chromosomes achieve a bipolar orientation, severely disrupt the partitioning of chromosomes in anaphase. Borealin depletion has little effect on histone H3 serine10 phosphorylation. These results implicate the chromosomal passenger holocomplex in the maintenance of spindle integrity and suggest that histone H3 serine10 phosphorylation is performed by an Aurora B–INCENP subcomplex.

scholarly journals APC/CCdh1 is required for the termination of chromosomal passenger complex activity upon mitotic exit

2020 ◽  
Vol 133 (18) ◽  
pp. jcs251314
Author(s):  
Takaaki Tsunematsu ◽  
Rieko Arakaki ◽  
Hidehiko Kawai ◽  
Jan Ruppert ◽  
Koichi Tsuneyama ◽  
...  
Keyword(s):  
Dna Replication ◽  
Kinase Activity ◽  
Mitotic Exit ◽  
Serum Starvation ◽  
Aurora B ◽  
Anaphase Promoting Complex ◽  
Complex Activity ◽  
Chromosomal Passenger Complex ◽  
N Terminus ◽  
Chromosomal Passenger

ABSTRACTDuring mitosis, the chromosomal passenger complex (CPC) ensures the faithful transmission of the genome. The CPC is composed of the enzymatic component Aurora B (AURKB) and the three regulatory and targeting components borealin, INCENP, and survivin (also known as BIRC5). Although the CPC is known to be involved in diverse mitotic events, it is still unclear how CPC function terminates after mitosis. Here we show that borealin is ubiquitylated by the anaphase promoting complex/cyclosome (APC/C) and its cofactor Cdh1 (also known as FZR1) and is subsequently degraded in G1 phase. Cdh1 binds to regions within the N terminus of borealin that act as a non-canonical degron. Aurora B has also been shown previously to be degraded by the APC/CCdh1 from late mitosis to G1. Indeed, Cdh1 depletion sustains an Aurora B activity with stable levels of borealin and Aurora B throughout the cell cycle, and causes reduced efficiency of DNA replication after release from serum starvation. Notably, inhibition of Aurora B kinase activity improves the efficiency of DNA replication in Cdh1-depleted cells. We thus propose that APC/CCdh1 terminates CPC activity upon mitotic exit and thereby contributes to proper control of DNA replication.

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