Calcineurin promotes APC/C activation at meiotic exit by acting on both XErp1 and Cdc20

Heim, Andreas; Tischer, Thomas; Mayer, Thomas

doi:10.15252/embr.201846433

Cited by 21 publications

(16 citation statements)

References 40 publications

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“…It has been established that PP2A-B56 localizes specifically to kinetochores and centromeres, participating in chromatid-microtubule interactions and silencing of the spindle assembly checkpoint 37,38 . Likely relating to this Mphase role, PP2A-B56 is involved in the metaphase II-arrest of Xenopus oocyte by regulating the APC/C inhibitor, XErp1 39,40 . These M-phase roles of PP2A-B56 are not directly connected to Cdk1 regulation and do not involve Arpp19.…”

Section: Discussionmentioning

confidence: 99%

The M-phase regulatory phosphatase PP2A-B55δ opposes protein kinase A on Arpp19 to initiate meiotic division

Lemonnier

Daldello

Poulhe

et al. 2019

Preprint

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Oocytes are held in meiotic prophase for prolonged periods until hormonal signals trigger meiotic divisions. Key players of M-phase entry are the opposing Cdk1 kinase and PP2A-B55δ phosphatase. In Xenopus, the protein Arpp19, phosphorylated at serine 67 by Greatwall, plays an essential role in inhibiting PP2A-B55δ, promoting Cdk1 activation.Furthermore Arpp19 has an earlier role in maintaining the prophase arrest through a second serine (S109) phosphorylated by PKA. Prophase release, induced by progesterone, relies on Arpp19 dephosphorylation at S109, owing to an unknown phosphatase. Here we identified this phosphatase as PP2A-B55δ. In prophase, PKA and PP2A-B55δ are simultaneously active, suggesting the presence of other important targets for both enzymes. The drop in PKA activity induced by progesterone decreases S109 phosphorylation, unlocking the prophase block. Hence, PP2A-B55δ acts critically on Arpp19 on two distinct sites, opposing PKA and Greatwall to orchestrate the prophase release and M-phase entry.

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Section: Discussionmentioning

confidence: 99%

The M-phase regulatory phosphatase PP2A-B55δ opposes protein kinase A on Arpp19 to initiate meiotic division

Lemonnier

Daldello

Poulhe

et al. 2019

Preprint

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“…Although the essential role of FBXO43 during mammal spermatogenesis has been identified in rats, mice, and horses (12,24,25), its mechanism of action remains elusive. In female mice, the FBXO43 protein binds directly to the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase and inhibits it, which maintains the arrest of oocytes at the second meiotic metaphase (9,11,26,27). Human FBXO43 is involved in the protein ubiquitination pathway.…”

Section: Discussionmentioning

confidence: 99%

A novel homozygous FBXO43 mutation associated with male infertility and teratozoospermia in a consanguineous Chinese family

Xie²,

Dong-yang

et al. 2019

Fertility and Sterility

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Objective: To identify the genetic causes of male infertility characterized by teratozoospermia. Design: Genetic studies. Setting: Medical university. Patient(s): Two infertile brothers with teratozoospermia in a consanguineous Chinese family, another 124 sporadic infertile male patients presenting with teratozoospermia, and 200 male controls with normal fertility. Invention(s): None. Main Outcome Measure(s): Whole exome sequencing and genotype analysis to identify the potential pathogenic mutation, Sanger sequencing to validate the mutation in family members, in silico structural modeling to predict the functional consequences of mutation, and targeted next-generation sequencing to validate the mutation in sporadic cases. Result(s): A novel homozygous nonsynonymous mutation (C1991T, p.G664D) in FBXO43 (F-box only protein 43) was observed in two brothers from a consanguineous Chinese family. The mutation was segregated with the disease phenotype and was predicted to be a disease causing protein by SIFT, PolyPhen-2, and Mutation Taster. An in silico mutant FBXO43 model predicts that the mutation p.G664D causes shortening of two b-sheets, an additional a-helix, and change in loops, which may result in loss of function of the protein. The homozygous mutation of FBXO43 was absent in the 1000 Genomes Project (1000 G) and the Exome Aggregation Consortium (ExAC) databases. Subsequent mutation screening of FBXO43 in a cohort of 124 cases identified four additional cases with heterozygous FBXO43 mutations. No mutations were found in FBXO43 in 200 fertile controls. Conclusion(s): The mutation in FBXO43 is a causative factor of male infertility and teratozoospermia.

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“…Its autoinhibition is governed by a threonine 286 residue. CaMKII is activated by the binding of Ca 2+ /CaM [41][42][43][44][45][46]. When CaMKII was phosphorylated at Thr286, it activates permanently.…”

Section: Discussionmentioning

confidence: 99%

Involvement of CaMKII in regulating the release of diplotene-arrested mouse oocytes by pAkt1 (Ser473)

Liu

Labbe

et al. 2019

Cell Cycle

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Calcium (Ca2+)/calmodulin-dependent protein kinase II (CaMKII) had been reported to play a role in the process of fertilization. However, the role of CaMKII in the release of diplotene-arrested oocytes is poorly understood. In this study, we explored the potential effect of CaMKII on Akt1 and the relationship among CaMKII, Akt1 and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) during the meiotic resumption of mouse oocytes. We found that inhibition of CaMKII aggravated diplotene arrest. We detected the expression and distribution of pCaMKII (Thr286), pAkt1 (Ser473), Cdc25B and pCdc2 (Tyr15) when oocytes were treated with KN-93, SH-6, LY294002 or PIP3, respectively. Our data showed that down-regulated CaMKII by KN-93 decreased the levels of pAkt1 (Ser473) and rearranged the distribution of pAkt1 (Ser473). Meanwhile, down-regulated pAkt1 (Ser473) by SH-6 also decreased the levels of pCaMKII (Thr286), Cdc25B and pCdc2 (Tyr15) significantly and rearranged the distributions of pCaMKII (Thr286). Furthermore, our data showed that exogenous PIP3 up-regulated GVBD rates significantly and increased the levels of pCaMKII (Thr286) and pAkt1 (Ser473). On the contrary, down-regulation of PIP3 by LY294002 decreased GVBD rates and the levels of pCaMKII (Thr286) and pAkt1 (Ser473), respectively. Our results showed that Akt1 and CaMKII regulated each other, and PIP3 may be involved in these regulations during the release of mouse oocytes from diplotene arrest.

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Calcineurin promotes APC/C activation at meiotic exit by acting on both XErp1 and Cdc20

Cited by 21 publications

References 40 publications

The M-phase regulatory phosphatase PP2A-B55δ opposes protein kinase A on Arpp19 to initiate meiotic division

The M-phase regulatory phosphatase PP2A-B55δ opposes protein kinase A on Arpp19 to initiate meiotic division

A novel homozygous FBXO43 mutation associated with male infertility and teratozoospermia in a consanguineous Chinese family

Involvement of CaMKII in regulating the release of diplotene-arrested mouse oocytes by pAkt1 (Ser473)

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