Feedback control of chromosome separation by a midzone Aurora B gradient

Afonso, Olga; Matos, Irina; Pereira, António J.; Aguiar, Paulo; Lampson, Michael A.; Maiato, Hélder

doi:10.1126/science.1251121

Cited by 115 publications

(215 citation statements)

References 29 publications

Supporting

Mentioning

190

Contrasting

Order By: Relevance

“…Furthermore, while failure in cytokinesis following depletion of bona-fide regulators such as Pavarotti results in cells with two comparably sized nuclei, Bin2-treated cells rarely exhibit the typical binucleate phenotype, but rather have single large nuclei or large nuclei with numerous smaller nuclei. Similar to prior observations (Afonso et al ., 2014), Bin2 addition in early anaphase led to rapid mitotic exit and the formation of a single large nucleus (Fig 3A, Supplemental Movies 8, 9). The fact that this Bin2-treated anaphase cell did not complete cytokinesis is likely due to the consequences of rapid mitotic exit as well as the positioning of the nucleus in the midzone position.…”

Section: Resultssupporting

confidence: 92%

“…ABK activity is essential for proper cytokinesis (Adams et al ., 2001, Echard et al ., 2004, Eggert et al ., 2004, Smurnyy et al ., 2010) and at anaphase onset the CPC complex re-localizes to the spindle midzone (Adams et al ., 2000), an area comprised of stable overlapping MTs. The midzone-associated CPC generates an activity gradient (Fuller et al ., 2008, Tan and Kapoor, 2011) that helps ensure complete sister chromatid separation (Afonso et al ., 2014), and that is proposed to contribute to cleavage furrow positioning (Adams et al ., 2000, Tan and Kapoor, 2011, Terada, 2001). Aurora A kinase is required for centrosome maturation, separation and function (Giet et al ., 2002, Glover et al ., 1995, Hannak et al ., 2001), proper kinetochore-MT attachment (Bakhoum et al ., 2014, Barisic et al ., 2014, Chmatal et al ., 2015, Ye et al ., 2015), chromosome segregation (Hegarat et al ., 2011), MT nucleation (Scrofani et al ., 2015) and robust assembly of midzone MTs (Lioutas and Vernos, 2013, Reboutier et al ., 2013).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Aurora A Kinase Amplifies a Midzone Phosphorylation Gradient to Promote High-Fidelity Cytokinesis

Torabi²,

Maresca

2016

The Biological Bulletin

View full text Add to dashboard Cite

Aurora B kinase (ABK) re-localizes from centromeres to the spindle midzone during cytokinesis where it is thought to provide a spatial cue for cytokinesis. While global ABK inhibition in Drosophila S2 cells results in macro- and multi-nucleated large cells, mis-localization of midzone ABK (mABK) by depletion of Subito (Drosophila MKLP2) does not cause notable cytokinesis defects. Subito depletion was; therefore, used to investigate the contribution of other molecules and redundant pathways to cytokinesis in the absence of mABK. Inhibiting potential polar relaxation pathways via removal of centrosomes (CNN RNAi) or a kinetochore-based phosphatase-gradient (Sds22 RNAi) did not result in cytokinesis defects on their own or in combination with loss of mABK. Disruption of Aurora A kinase (AAK) activity resulted in midzone assembly defects but did not significantly affect contractile ring positioning or cytokinesis. Live-cell imaging of a FRET-based aurora kinase phosphorylation sensor revealed that midzone substrates were less phosphorylated in AAK-inhibited cells, despite the fact that midzone levels of active phosphorylated ABK (pABK) were normal. Interestingly, an increased number of binucleated cells were observed following AAK inhibition in the absence of mABK. The data suggest that equatorial stimulation rather than polar relaxation mechanisms are the major determinants of contractile ring positioning and high-fidelity cytokinesis in Drosophila S2 cells. Furthermore, we propose that equatorial stimulation is mediated primarily by the delivery of factors to the cortex by non-centrosomal microtubules (MTs) as well as a midzone-derived phosphorylation gradient that is amplified by the concerted activities of mABK and a soluble pool of AAK.

show abstract

Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Aurora A Kinase Amplifies a Midzone Phosphorylation Gradient to Promote High-Fidelity Cytokinesis

Torabi²,

Maresca

2016

The Biological Bulletin

View full text Add to dashboard Cite

show abstract

“…PP1c docked on MEL-28 at kinetochores in anaphase may also help counter Aurora B kinase localized at the midzone, which is proposed to restrict nuclear envelope reformation (Afonso et al, 2014). More speculatively, outer kinetochore disassembly by MEL-28-PP1c may be important for replication of centromeric chromatin, whose assembly is coupled to M-phase exit in many species (McKinley and Cheeseman, 2016).…”

Section: Discussionmentioning

confidence: 99%

A Nucleoporin Docks Protein Phosphatase 1 to Direct Meiotic Chromosome Segregation and Nuclear Assembly

et al. 2016

View full text Add to dashboard Cite

SUMMARY During M-phase entry in metazoans with open mitosis, the concerted action of mitotic kinases disassembles nuclei and promotes assembly of kinetochores—the primary microtubule attachment sites on chromosomes. At M-phase exit, these major changes in cellular architecture must be reversed. Here, we show that the conserved kinetochore-localized nucleoporin MEL-28/ELYS docks the catalytic subunit of protein phosphatase 1 (PP1c) to direct kinetochore disassembly-dependent chromosome segregation during oocyte meiosis I, and nuclear assembly during the transition from M-phase to interphase. During oocyte meiosis I, MEL-28-PP1c disassembles kinetochores in a timely manner to promote elongation of the acentrosomal spindles that segregate homologous chromosomes. During nuclear assembly, MEL-28 recruits PP1c to the periphery of decondensed chromatin where it directs formation of a functional nuclear compartment. Thus, a pool of phosphatase activity associated with a kinetochore-localized nucleoporin contributes to two key events that occur during M-phase exit in metazoans: kinetochore disassembly and nuclear reassembly.

show abstract

“…The role of PP2A in this process is less characterized. Nonetheless, a recent study showed that a midzone-associated Aurora B gradient monitors chromosome position along the division axis and to prevent premature chromosome decondensation by retaining Condensin I until effective separation of sister chromatids is achieved (Afonso et al ., 2014). Both PP1 and PP2A phosphatases counteract this gradient and promoted chromosome decondensation (Afonso et al ., 2014).…”

Section: Mitosis: Pp2a As a Gatekeeper From Mitotic Entry To Mitotic mentioning

confidence: 99%

PP2A as a master regulator of the cell cycle

Wlodarchak

Xing

2016

Critical Reviews in Biochemistry and Molecular Biology

306

273

View full text Add to dashboard Cite

Protein phosphatase 2A (PP2A) plays a critical multi-faceted role in the regulation of the cell cycle. It is known to dephosphorylate over 300 substrates involved in the cell cycle, regulating almost all major pathways and cell cycle checkpoints. PP2A is involved in such diverse processes by the formation of structurally distinct families of holoenzymes, which are regulated spatially and temporally by specific regulators. Here, we review the involvement of PP2A in the regulation of three cell signaling pathways: wnt, mTOR and MAP kinase, as well as the G1→S transition, DNA synthesis and mitotic initiation. These processes are all crucial for proper cell survival and proliferation and are often deregulated in cancer and other diseases.

show abstract

Feedback control of chromosome separation by a midzone Aurora B gradient

Cited by 115 publications

References 29 publications

Aurora A Kinase Amplifies a Midzone Phosphorylation Gradient to Promote High-Fidelity Cytokinesis

Aurora A Kinase Amplifies a Midzone Phosphorylation Gradient to Promote High-Fidelity Cytokinesis

A Nucleoporin Docks Protein Phosphatase 1 to Direct Meiotic Chromosome Segregation and Nuclear Assembly

PP2A as a master regulator of the cell cycle

Contact Info

Product

Resources

About