Endogenous regulators of protein phosphatase-1 during mouse oocyte development and meiosis

Wang, Xia; Swain, Jason E.; Liu, Xiao-Tie; Ohl, Dana A.; Smith, Gary D.

doi:10.1530/rep.1.00173

Cited by 22 publications

(25 citation statements)

References 45 publications

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“…This result indicates that CDC25 activity is required in addition to Wee1B downregulation for the meiotic resumption. Because the suppression of CDC25 activity by PKA has been reported, [50][51][52] the low GVBD rate of the pigWee1B-downregulated oocytes might be attributed to the suppression of CDC25 activity by the high cAMP concentration.…”

Section: Discussionmentioning

confidence: 93%

Critical effect of pigWee1B on the regulation of meiotic resumption in porcine immature oocytes

Shimaoka

Nishimura²,

Kanô³

et al. 2009

Cell Cycle

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Porcine immature oocytes require protein synthesis for meiotic resumption, thus the importance of Cdc2 inhibitory phosphorylation in their meiotic arrest remains controversial. We examined the involvement of Cdc2 phosphorylation in the meiotic arrest of porcine oocytes with a special focus on Wee1B, an oocyte-specific Wee1 family member recently reported in mouse oocytes. We cloned a Wee1B homologue of pig by RT-PCR followed by 5'-and 3'-RACE. Overexpression of pigWee1B in porcine immature oocytes by the injection of pigWee1B mRNA almost completely blocked the germinal vesicle breakdown (GVBD) under the low cAMP concentration, which could not block their spontaneous meiotic resumption by itself. The MPF activation and cyclin B synthesis were inhibited in these oocytes. Conversely, downregulation of pigWee1B expression by the injection of specific antisense mRNA induced GVBD in the oocytes, the spontaneous meiotic resumption of which was blocked by the high concentration of cAMP (dbcAMP). In these oocytes, the MPF activity was elevated and cyclin B was accumulated. Downregulation of pigMyt1, another Wee1 family member, could not induce the GVBD under the same condition. The inhibition of tyrosine phosphatase by vanadate blocked the GVBD even in the pigWee1B-downregulated oocytes. These results suggest that the inhibitory phosphorylation of CDC2, which is catalyzed by pigWee1B, but not pigMyt1, is involved in the meiotic arrest of porcine oocytes, and that the inactivation of Wee1B in combination with the phosphatase activation induces the conversion of pre-MPF to the active MPF and starts the cyclin B synthesis, follwed by a further increase of MPF and meiotic resumption.

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Section: Discussionmentioning

confidence: 93%

Critical effect of pigWee1B on the regulation of meiotic resumption in porcine immature oocytes

Shimaoka

Nishimura²,

Kanô³

et al. 2009

Cell Cycle

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“…An involvement of okadaic acid (OA)-sensitive PP has been demonstrated during oocyte maturation in starfish, Xenopus and mammals (Huchon et al, 1981;Bornslaeger et al, 1986;Goris et al, 1989;Pondaven et al, 1989;Rime and Ozon, 1990;Schwartz and Schultz, 1991;Lu et al, 2001;Wang et al, 2004). Evidence for a crosstalk between cAMP-PKA and OA-sensitive PP was presented as well (Schwartz and Schultz, 1991;Lu et al, 2001).…”

Section: Introductionmentioning

confidence: 97%

2-hydroxyestradiol-17β-induced oocyte maturation: involvement of cAMP–protein kinase A and okadaic acid-sensitive protein phosphatases,and their interplay in oocyte maturation in the catfishHeteropneustes fossilis

Mishra

Joy

2006

Journal of Experimental Biology

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SUMMARY In Heteropneustes fossilis, in vitro incubation of postvitellogenic follicles with 2-hydroxyestradiol-17β(2-OHE2, 5 μmol l–1) decreased significantly the total cAMP level, concomitant with germinal vesicle breakdown (GVBD). The incubation of the follicles with cAMP or cAMP-elevating drugs[phosphodiesterase (PDE) inhibitors], such as IBMX(3-isobutyl-1-methyl-xanthine), theophylline and caffeine, inhibited the 2-OHE2-induced GVBD in a concentration-dependent manner. The magnitude of the response varied: both cAMP and IBMX were effective at all concentrations (0.1–2.0 mmol l–1), followed by theophylline (0.5–2.0 mmol l–1) and caffeine(1–2.0 mmol l–1). The protein kinase A (PKA) inhibitor H89 stimulated oocyte maturation in a concentration-dependent manner. However,when co-incubated with 2-OHE2 for 24 h it produced a biphasic effect: low concentrations (0.1 and 1.0 μmol l–1) did not alter the 2-OHE2-induced GVBD, but high concentrations (5 and 10μmol l–1) inhibited it. The incubation of the follicles with H89 lowered the inhibitory effect of IBMX on the 2-OHE2-induced GVBD. The incubation of the follicles with okadaic acid (OA), a protein phosphatase 1 and 2A inhibitor did not affect GVBD but when co-incubated with 2-OHE2, it enhanced the GVBD response. OA reversed the inhibitory effect of IBMX. The results suggest that OA may overcome the inhibition of 2-OHE2-induced GVBD by IBMX at a step distal to the cAMP–PKA pathway.

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“…In metII mouse eggs, OA induces spindle lengthening (26) and has been reported to block meiotic exit (27). However, it is clear that mouse oocytes contain PP1 in addition to PP2A, and some of the effects of OA on prophase I mouse oocytes may be due to PP1 inhibition (28,29).In this study, we decided to further examine the cell cycle effects of OA on mouse metII eggs. We wanted to determine the outcome of OA addition on cyclin B1 and securin degradation specifically because PP2A is needed in Xenopus eggs to hydrolyze CDK1 phosphorylation sites on Emi2, thereby strengthening Emi2 interaction with the APC/C (30 -32).…”

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confidence: 99%

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confidence: 99%

Essential Role of Protein Phosphatase 2A in Metaphase II Arrest and Activation of Mouse Eggs Shown by Okadaic Acid, Dominant Negative Protein Phosphatase 2A, and FTY720

Chang¹,

Jennings

Stewart

et al. 2011

Journal of Biological Chemistry

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Vertebrate eggs arrest at second meiotic metaphase. The fertilizing sperm causes meiotic exit through Ca 2؉ -mediated activation of the anaphase-promoting complex/cyclosome (APC/ C). Although the loss in activity of the M-phase kinase CDK1 is known to be an essential downstream event of this process, the contribution of phosphatases to arrest and meiotic resumption is less apparent, especially in mammals. Therefore, we explored the role of protein phosphatase 2A (PP2A) in mouse eggs using pharmacological inhibition and activation as well as a functionally dominant-negative catalytic PP2A subunit (dn-PP2Ac-L199P) coupled with live cell imaging. We observed that PP2A inhibition using okadaic acid induced events normally observed at fertilization: degradation of the APC/C substrates cyclin B1 and securin resulting from loss of the APC/C inhibitor Emi2. Although sister chromatids separated, chromatin remained condensed, and polar body extrusion was blocked as a result of a rapid spindle disruption, which could be ameliorated by nondegradable cyclin B1, suggesting that spindle integrity was affected by CDK1 loss. Similar cell cycle effects to okadaic acid were also observed using dominant-negative PP2Ac. Preincubation of eggs with the PP2A activator FTY720 could block many of the actions of okadaic acid, including Emi2, cyclin B1, and securin degradation and sister chromatid separation. Therefore, in conclusion, we used okadaic acid, dn-PP2Ac-L199P, and FTY720 on mouse eggs to demonstrate that PP2A is needed to for both continued metaphase arrest and successful exit from meiosis.Mouse eggs, as with most vertebrates, arrest at metaphase of the second meiotic division (metII) 3 until fertilized (1-3). Crucial to this arrest is inhibition of the anaphase-promoting complex/cyclosome (APC/C), thereby preventing cyclin B1 and securin degradation and so maintaining high CDK1 kinase (also known as Maturation Promoting Factor, MPF; CDK1/cyclin B1) and low separase (ESPL1) protease activities, respectively (1, 4 -6). At fertilization, a sperm-derived Ca 2ϩ signal causes loss of the APC/C inhibitor Emi2, resulting in a drop in CDK1 activity by cyclin B1 degradation and associated anaphase, driven by the protease separase (7-10).For successful exit from metaphase in either mitosis or meiosis, it is now becoming clear that phosphatase activity is needed to dephosphorylate CDK1 substrates. In Xenopus eggs, calcineurin activity is essential in the process of exit from metII arrest, but this function is not conserved in mouse eggs (11-13). Mammalian eggs may deviate or differ from Xenopus, so it is not always possible to extrapolate across species with accuracy, and indeed this lack of conservation is observed in more than one aspect of cell cycle control (13-15). Instead, the exit of the mouse egg from metII arrest may more closely match mitotic exit in somatic cells and so rely on phosphatase activity from a member of the protein phosphatase 2A (PP2A) family (16 -20).The heterotrimeric nature of the PP2A holoenzyme, coupled with a...

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Endogenous regulators of protein phosphatase-1 during mouse oocyte development and meiosis

Cited by 22 publications

References 45 publications

Critical effect of pigWee1B on the regulation of meiotic resumption in porcine immature oocytes

Critical effect of pigWee1B on the regulation of meiotic resumption in porcine immature oocytes

2-hydroxyestradiol-17β-induced oocyte maturation: involvement of cAMP–protein kinase A and okadaic acid-sensitive protein phosphatases,and their interplay in oocyte maturation in the catfishHeteropneustes fossilis

Essential Role of Protein Phosphatase 2A in Metaphase II Arrest and Activation of Mouse Eggs Shown by Okadaic Acid, Dominant Negative Protein Phosphatase 2A, and FTY720

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