Cyclin B3 implements timely vertebrate oocyte arrest for fertilization

Bouftas, Nora; Schneider, Lena; Halder, Marc; Demmig, Rebecca; Baack, Martina; Cladière, Damien; Walter, Melanie; Abdallah, Hiba Al; Kleinhempel, Camilla; Messaritaki, Ria; Müller, Janina; Passarelli, Francesca; Wehrle, Patrick; Heim, Andreas; Wassmann, Katja; Mayer, Thomas

doi:10.1016/j.devcel.2022.09.005

Cited by 8 publications

(28 citation statements)

References 48 publications

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“…For CSF preparation, frogs were primed with injection of 20 U human chorionic gonadotropin (hCG) 3 to 14 days previous to injection of 500 U hCG to induce egg laying according to approved proposal (file number: 35-9185.81/G-22/081). Further CSF preparation was performed by step wise centrifugation of dejelled eggs (described in detail in Bouftas et al 2022).…”

Section: Xenopus Laevis Stage VI Oocytes and Csf Extractmentioning

confidence: 99%

“…Fertilization triggers degradation of XErp1/Emi2, thereby resulting in APC/C activation and, hence, in exit from MII (Hansen et al , 2006; Liu et al , 2006; Rauh et al , 2005). Recently, we could dissect cyclin B3’s essential function in female meiosis by demonstrating that it targets the APC/C inhibitor XErp1/Emi2 for proteasomal degradation in meiosis I (Bouftas et al , 2022). This mechanism, which is conserved from frog to mouse and includes Plk1 (Polo-like kinase 1), is essential to keep the levels of XErp1/Emi2 during meiosis I below the threshold critical for APC/C inhibition (Bouftas et al ., 2022; Meng et al , 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we could dissect cyclin B3’s essential function in female meiosis by demonstrating that it targets the APC/C inhibitor XErp1/Emi2 for proteasomal degradation in meiosis I (Bouftas et al , 2022). This mechanism, which is conserved from frog to mouse and includes Plk1 (Polo-like kinase 1), is essential to keep the levels of XErp1/Emi2 during meiosis I below the threshold critical for APC/C inhibition (Bouftas et al ., 2022; Meng et al , 2020). Destruction of cyclin B3 during exit from MI allows XErp1/Emi2 accumulation resulting in APC/C inhibition essential for entry into MII.…”

Section: Introductionmentioning

confidence: 99%

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A phosphate-binding pocket in cyclin B3 is essential for XErp1/ Emi2 degradation in meiosis I

Demmig,

Schäfer,

Johannes

et al. 2024

Preprint

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To ensure the correct euploid state of embryos, it is essential that vertebrate oocytes await fertilization arrested at metaphase of meiosis II. This MII arrest is mediated by XErp1/Emi2, which inhibits the ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome). Cyclin B3 in complex with Cdk1 (cyclin-dependent kinase 1) is essential to prevent an untimely arrest of vertebrate oocytes in meiosis I by targeting XErp1/Emi2 for degradation. Yet, the molecular mechanism of XErp1/Emi2 degradation in MI is not well understood. Here, by combining TRIM-Away in oocytes with egg extract and in vitro studies, we demonstrate that a hitherto unknown phosphate-binding pocket in cyclin B3 is essential for efficient XErp1/Emi2 degradation in meiosis I. This pocket enables Cdk1/cyclin B3 to bind pre-phosphorylated XErp1/Emi2 facilitating further phosphorylation events, which ultimately target XErp1/Emi2 for degradation in a Plk1 (Polo-like kinase 1) dependent manner. Key elements of this degradative mechanism are conserved in frog and mouse. Our studies identify a novel, evolutionarily conserved determinant of Cdk/cyclin substrate specificity essential to prevent an untimely oocyte arrest at meiosis I with catastrophic consequences upon fertilization.

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Section: Xenopus Laevis Stage VI Oocytes and Csf Extractmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A phosphate-binding pocket in cyclin B3 is essential for XErp1/ Emi2 degradation in meiosis I

Demmig,

Schäfer,

Johannes

et al. 2024

Preprint

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“…Elle est présente tout au long de la méiose I, puis dégradée après l'anaphase de méiose I par un mécanisme impliquant le motif d'ubiquitination par l'APC (D-box), commun aux cyclines B [2,5]. En revanche, elle ne s'accumule pas en méiose II [6]. Lorsqu'elle est exprimée artificiellement à contretemps dans les ovocytes de souris bloqués en métaphase II, la cycline B3 déclenche l'anaphase de méiose II sans fécondation [5,6].…”

Section: La Cycline B3 Verrou De La Méiose Femelle En Attendant La Fé...unclassified

“…En revanche, elle ne s'accumule pas en méiose II [6]. Lorsqu'elle est exprimée artificiellement à contretemps dans les ovocytes de souris bloqués en métaphase II, la cycline B3 déclenche l'anaphase de méiose II sans fécondation [5,6]. La dérégulation de la cycline B3 a donc des effets biologiques divergents de ceux décrits pour les cyclines B1/B2, dont la surexpression bloque l'ovocyte en métaphase I et dont l'invalidation inhibe la progression en méiose II [1].…”

Section: La Cycline B3 Verrou De La Méiose Femelle En Attendant La Fé...unclassified

La cycline B3, verrou de la méiose femelle en attendant la fécondation

Dupré

Wassmann

2023

Med Sci (Paris)

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Cyclin B3 is a dominant fast-acting cyclin that drives rapid early embryonic mitoses

Lara-Gonzalez,

Variyar,

Moghareh

et al. 2024

Journal of Cell Biology

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Mitosis in early embryos often proceeds at a rapid pace, but how this pace is achieved is not understood. Here, we show that cyclin B3 is the dominant driver of rapid embryonic mitoses in the C. elegans embryo. Cyclins B1 and B2 support slow mitosis (NEBD to anaphase ∼600 s), but the presence of cyclin B3 dominantly drives the approximately threefold faster mitosis observed in wildtype. Multiple mitotic events are slowed down in cyclin B1 and B2–driven mitosis, and cyclin B3–associated Cdk1 H1 kinase activity is ∼25-fold more active than cyclin B1–associated Cdk1. Addition of cyclin B1 to fast cyclin B3–only mitosis introduces an ∼60-s delay between completion of chromosome alignment and anaphase onset; this delay, which is important for segregation fidelity, is dependent on inhibitory phosphorylation of the anaphase activator Cdc20. Thus, cyclin B3 dominance, coupled to a cyclin B1–dependent delay that acts via Cdc20 phosphorylation, sets the rapid pace and ensures mitotic fidelity in the early C. elegans embryo.

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Cyclin B3 implements timely vertebrate oocyte arrest for fertilization

Cited by 8 publications

References 48 publications

A phosphate-binding pocket in cyclin B3 is essential for XErp1/ Emi2 degradation in meiosis I

A phosphate-binding pocket in cyclin B3 is essential for XErp1/ Emi2 degradation in meiosis I

La cycline B3, verrou de la méiose femelle en attendant la fécondation

Cyclin B3 is a dominant fast-acting cyclin that drives rapid early embryonic mitoses

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