title: α-endosulfine (ENSA) regulates exit from prophase I arrest in mouse oocytes.
abstract: Mammalian oocytes in ovarian follicles are arrested in meiosis at prophase I. This arrest is maintained until ovulation, upon which the oocyte exits from this arrest, progresses through meiosis I and to metaphase of meiosis II. The progression from prophase I to metaphase II, known as meiotic maturation, is mediated by signals that coordinate these transitions in the life of the oocyte. ENSA (α-endosulfine) and ARPP19 (cAMP-regulated phosphoprotein-19) have emerged as regulators of M-phase, with function in inhibition of protein phosphatase 2A (PP2A) activity. Inhibition of PP2A maintains the phosphorylated state of CDK1 substrates, thus allowing progression into and/or maintenance of an M-phase state. We show here ENSA in mouse oocytes plays a key role in the progression from prophase I arrest into M-phase of meiosis I. The majority of ENSA-deficient oocytes fail to exit from prophase I arrest. This function of ENSA in oocytes is dependent on PP2A, and specifically on the regulatory subunit PPP2R2D (also known as B55δ). Treatment of ENSA-deficient oocytes with Okadaic acid to inhibit PP2A rescues the defect in meiotic progression, with Okadaic acid-treated, ENSA-deficient oocytes being able to exit from prophase I arrest. Similarly, oocytes deficient in both ENSA and PPP2R2D are able to exit from prophase I arrest to an extent similar to wild-type oocytes. These data are evidence of a role for ENSA in regulating meiotic maturation in mammalian oocytes, and also have potential relevance to human oocyte biology, as mouse and human have genes encoding both Arpp19 and Ensa.
authors.affiliation: Department of Biochemistry and Molecular Biology; Bloomberg School of Public Health; Johns Hopkins University; Baltimore, MD USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Matthews
authors.affiliation: Department of Biochemistry and Molecular Biology; Bloomberg School of Public Health; Johns Hopkins University; Baltimore, MD USA.
authors.forename: Janice P
authors.initials: JP
authors.lastname: Evans
mesh_terms: D000818:Animals; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins; D059566:M Phase Cell Cycle Checkpoints; D049469:Meiotic Prophase I / Q000502:physiology*; D051379:Mice; D019319:Okadaic Acid / Q000494:pharmacology; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010750:Phosphoproteins; C064321:cyclic AMP-regulated phosphoprotein 19; C075663:endosulfine; D019319:Okadaic Acid; C586425:Ppp2r2d protein, mouse; D054648:Protein Phosphatase 2
keywords: ARPP19; Greatwall; MASTL; PP2A; alpha-endosulfine; meiosis; meiotic maturation; oocyte