BUB-1 targets PP2A:B56 to regulate chromosome congression during meiosis I in<i>C. elegans</i>oocytes

Borja, Laura Bel; Soubigou, Flavie; Taylor, Samuel J P; Bringas, Conchita Fraguas; Budrewicz, Jacqueline; Lara-González, Pablo; Sorensen-Turpin, Christopher G.; Bembenek, Joshua N.; Cheerambathur, Dhanya K.; Pelisch, Federico

doi:10.1101/2020.06.12.148254

Cited by 3 publications

(5 citation statements)

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“…KNL-1, BUB-1, CLS-2, and other cell division proteins have been described previously as being present in roughly linear cortical structures that also are present throughout the assembling oocyte meiotic spindle. These structures previously have been referred to both as rods and as linear elements (17)(18)(19)(20), and one component can indeed form linear filaments in vitro and greatly extended linear structures when overexpressed in vivo (33). Here we refer to these cortical structures as patches, given their less linear appearance as meiosis I proceeds, and to distinguish them from the more linear spindle-associated elements.…”

Section: Discussionmentioning

confidence: 97%

“…During oocyte meiotic cell division, CLS-2 localizes to spindle microtubules, to kinetochores, and to small patches, also called linear elements or rods, distributed throughout the assembling spindle and the oocyte cortex (Monen et al 2005; Dumont, Oegema, and Desai 2010; Bel Borja et al 2020). We previously reported two prominent defects during meiosis I cell division in mutant oocytes produced by worms homozygous for null mutations in the cls-2 locus (13).…”

Section: Introductionmentioning

confidence: 99%

“…Like other outer kinetochore sub-complexes, the BUB-1/HCP-1/2/CLS-2 sub-complex depends on the kinetochore scaffolding protein KNL-1 for its kinetochore localization (19,30). Intriguingly, like CLS-2, both KNL-1 and BUB-1 also localize to linear elements that are enriched within the assembling spindle and are distributed throughout the oocyte cortex during meiosis I cell division (18)(19)(20). While all three proteins co-localize to kinetochores, it is not known whether they also co-localize within the patches, or linear elements, distributed throughout the oocyte cortex.…”

Section: Introductionmentioning

confidence: 99%

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Cortical microtubules oppose actomyosin-driven membrane ingression duringC. elegansmeiosis I polar body extrusion

Quiogue¹,

Sumiyoshi²,

Fries

et al. 2023

Preprint

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DuringC. elegansoocyte meiosis I, cortical actomyosin is locally remodeled to assemble a contractile ring near the spindle. In contrast to mitosis, when most cortical actomyosin converges into a contractile ring, the small oocyte ring forms within and remains part of a much larger and actively contractile cortical actomyosin network. This network both mediates contractile ring dynamics and generates shallow ingressions throughout the oocyte cortex during polar body extrusion. Based on our analysis of requirements for CLS-2, a member of the CLASP family of proteins that stabilize microtubules, we recently proposed that a balance of actomyosin-mediated tension and microtubule-mediated stiffness are required for contractile ring assembly within the oocyte cortical actomyosin network. Here, using live cell imaging and fluorescent protein fusions, we show that CLS-2 is part of a complex of kinetochore proteins, including the scaffold KNL-1 and the kinase BUB-1, that also co-localize to patches distributed throughout the oocyte cortex during meiosis I. By reducing their function, we further show that KNL-1 and BUB-1, like CLS-2, are required for cortical microtubule stability, to limit membrane ingression throughout the oocyte, and for meiotic contractile ring assembly and polar body extrusion. Moreover, nocodazole or taxol treatment to destabilize or stabilize oocyte microtubules, respectively, leads to excess or decreased membrane ingression throughout the oocyte and defective polar body extrusion. Finally, genetic backgrounds that elevate cortical microtubule levels suppress the excess membrane ingression in cls-2 mutant oocytes. These results support our hypothesis that CLS-2, as part of a sub-complex of kinetochore proteins that also co-localize to patches throughout the oocyte cortex, stabilizes microtubules to stiffen the oocyte cortex and limit membrane ingression throughout the oocyte, thereby facilitating contractile ring dynamics and the successful completion of polar body extrusion during meiosis I.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cortical microtubules oppose actomyosin-driven membrane ingression duringC. elegansmeiosis I polar body extrusion

Quiogue¹,

Sumiyoshi²,

Fries

et al. 2023

Preprint

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show abstract

“…Furthermore, in C. elegans, BUB1-bound PLK1 phosphorylates the BUB1 ABBA motif to both enhance CDC20 binding and promote CDC20 dephosphorylation/activation, which together helps to activate the APC/C and allow timely mitotic exit (Houston et al, 2023). C. elegans BUB1 contains similar PLK1-and PP2Abinding motifs to BUBR1, and these are important for chromosome alignment and segregation during meiosis I (Bel Borja et al, 2020;Taylor et al, 2023). Cross-talk between PLK1 and PP2A has not been evaluated in worms, but it is notable that a PLK1 phosphorylation site is preserved in the PP2A-B56-binding site.…”

Section: Negative Feedbackmentioning

confidence: 99%

A bifunctional kinase–phosphatase module balances mitotic checkpoint strength and kinetochore–microtubule attachment stability

Corno,

Cordeiro,

Allan

et al. 2023

The EMBO Journal

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Two major mechanisms safeguard genome stability during mitosis: the mitotic checkpoint delays mitosis until all chromosomes have attached to microtubules, and the kinetochore–microtubule error‐correction pathway keeps this attachment process free from errors. We demonstrate here that the optimal strength and dynamics of these processes are set by a kinase–phosphatase pair (PLK1‐PP2A) that engage in negative feedback from adjacent phospho‐binding motifs on the BUB complex. Uncoupling this feedback to skew the balance towards PLK1 produces a strong checkpoint, hypostable microtubule attachments and mitotic delays. Conversely, skewing the balance towards PP2A causes a weak checkpoint, hyperstable microtubule attachments and chromosome segregation errors. These phenotypes are associated with altered BUB complex recruitment to KNL1‐MELT motifs, implicating PLK1‐PP2A in controlling auto‐amplification of MELT phosphorylation. In support, KNL1‐BUB disassembly becomes contingent on PLK1 inhibition when KNL1 is engineered to contain excess MELT motifs. This elevates BUB‐PLK1/PP2A complex levels on metaphase kinetochores, stabilises kinetochore–microtubule attachments, induces chromosome segregation defects and prevents KNL1‐BUB disassembly at anaphase. Together, these data demonstrate how a bifunctional PLK1/PP2A module has evolved together with the MELT motifs to optimise BUB complex dynamics and ensure accurate chromosome segregation.

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“…A recent study found that PP2A is necessary for female meiotic progression, such as spindle assembly and chromosome segregation. The mechanism is that BUB-1 targets PP2A-B′56 via a conserved LxxIxE motif and this regulation is necessary for correct meiotic progression ( Bel Borja et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Critical Functions of PP2A-Like Protein Phosphotases in Regulating Meiotic Progression

Lei

Qian

Sun

2021

Front. Cell Dev. Biol.

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Meiosis is essential to the continuity of life in sexually-reproducing organisms through the formation of haploid gametes. Unlike somatic cells, the germ cells undergo two successive rounds of meiotic divisions after a single cycle of DNA replication, resulting in the decrease in ploidy. In humans, errors in meiotic progression can cause infertility and birth defects. Post-translational modifications, such as phosphorylation, ubiquitylation and sumoylation have emerged as important regulatory events in meiosis. There are dynamic equilibrium of protein phosphorylation and protein dephosphorylation in meiotic cell cycle process, regulated by a conservative series of protein kinases and protein phosphatases. Among these protein phosphatases, PP2A, PP4, and PP6 constitute the PP2A-like subfamily within the serine/threonine protein phosphatase family. Herein, we review recent discoveries and explore the role of PP2A-like protein phosphatases during meiotic progression.

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BUB-1 targets PP2A:B56 to regulate chromosome congression during meiosis I inC. elegansoocytes

Cited by 3 publications

References 82 publications

Cortical microtubules oppose actomyosin-driven membrane ingression duringC. elegansmeiosis I polar body extrusion

Cortical microtubules oppose actomyosin-driven membrane ingression duringC. elegansmeiosis I polar body extrusion

A bifunctional kinase–phosphatase module balances mitotic checkpoint strength and kinetochore–microtubule attachment stability

Critical Functions of PP2A-Like Protein Phosphotases in Regulating Meiotic Progression

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