title: Dephosphorylation and inactivation of NPR2 guanylyl cyclase in granulosa cells contributes to the LH-induced decrease in cGMP that causes resumption of meiosis in rat oocytes.
abstract: In mammals, the meiotic cell cycle of oocytes starts during embryogenesis and then pauses. Much later, in preparation for fertilization, oocytes within preovulatory follicles resume meiosis in response to luteinizing hormone (LH). Before LH stimulation, the arrest is maintained by diffusion of cyclic (c)GMP into the oocyte from the surrounding granulosa cells, where it is produced by the guanylyl cyclase natriuretic peptide receptor 2 (NPR2). LH rapidly reduces the production of cGMP, but how this occurs is unknown. Here, using rat follicles, we show that within 10 min, LH signaling causes dephosphorylation and inactivation of NPR2 through a process that requires the activity of phosphoprotein phosphatase (PPP)-family members. The rapid dephosphorylation of NPR2 is accompanied by a rapid phosphorylation of the cGMP phosphodiesterase PDE5, an enzyme whose activity is increased upon phosphorylation. Later, levels of the NPR2 agonist C-type natriuretic peptide decrease in the follicle, and these sequential events contribute to the decrease in cGMP that causes meiosis to resume in the oocyte.
authors.affiliation: Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Egbert
authors.affiliation: Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Leia C
authors.initials: LC
authors.lastname: Shuhaibar
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Edmund
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Dusty A
authors.initials: DA
authors.lastname: Van Helden
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Jerid W
authors.initials: JW
authors.lastname: Robinson
authors.affiliation: Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Tracy F
authors.initials: TF
authors.lastname: Uliasz
authors.affiliation: Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Baena
authors.affiliation: Bayer Pharma AG, Pharma Research Center, Wuppertal D-42096, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Geerts
authors.affiliation: Bayer Pharma AG, Pharma Research Center, Wuppertal D-42096, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Wunder
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA potter@umn.edu ljaffe@uchc.edu.
authors.forename: Lincoln R
authors.initials: LR
authors.lastname: Potter
authors.affiliation: Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA potter@umn.edu ljaffe@uchc.edu.
authors.forename: Laurinda A
authors.initials: LA
authors.lastname: Jaffe
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D006152:Cyclic GMP / Q000378:metabolism*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism*; D047468:Immunoprecipitation; D007986:Luteinizing Hormone / Q000378:metabolism*; D008540:Meiosis / Q000502:physiology*; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism; D009865:Oocytes / Q000502:physiology*; D006080:Ovarian Follicle / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000819:agonists / Q000378:metabolism*; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D006152:Cyclic GMP; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D007986:Luteinizing Hormone; D020098:Natriuretic Peptide, C-Type; D010749:Phosphoprotein Phosphatases; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B
keywords: Guanylyl cyclase; Luteinizing hormone; Meiosis; Natriuretic peptide receptor; Ovarian follicle; Phosphorylation