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

Jeremy R. Egbert, Leia C. Shuhaibar, Aaron B. Edmund, Dusty A. Van Helden, Jerid W. Robinson, Tracy F. Uliasz, Valentina Baena, Andreas Geerts, Frank Wunder, Lincoln R. Potter, Laurinda A. Jaffe

Research output: Contribution to journalArticle

47 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3594-3604
Number of pages11
JournalDevelopment (Cambridge)
Volume141
Issue number18
DOIs
StatePublished - Sep 2014

Fingerprint

Natriuretic Peptides
Peptide Receptors
Granulosa Cells
Guanylate Cyclase
Meiosis
Luteinizing Hormone
peptide
Oocytes
hormone
cause
family member
Phosphorylation
C-Type Natriuretic Peptide
Type 5 Cyclic Nucleotide Phosphodiesterases
event
Phosphoprotein Phosphatases
Cyclic GMP
Fertilization
Embryonic Development
Mammals

Keywords

  • Guanylyl cyclase
  • Luteinizing hormone
  • Meiosis
  • Natriuretic peptide receptor
  • Ovarian follicle
  • Phosphorylation

Cite this

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. / Egbert, Jeremy R.; Shuhaibar, Leia C.; Edmund, Aaron B.; Van Helden, Dusty A.; Robinson, Jerid W.; Uliasz, Tracy F.; Baena, Valentina; Geerts, Andreas; Wunder, Frank; Potter, Lincoln R.; Jaffe, Laurinda A.

In: Development (Cambridge), Vol. 141, No. 18, 09.2014, p. 3594-3604.

Research output: Contribution to journalArticle

Egbert, Jeremy R. ; Shuhaibar, Leia C. ; Edmund, Aaron B. ; Van Helden, Dusty A. ; Robinson, Jerid W. ; Uliasz, Tracy F. ; Baena, Valentina ; Geerts, Andreas ; Wunder, Frank ; Potter, Lincoln R. ; Jaffe, Laurinda A. / 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. In: Development (Cambridge). 2014 ; Vol. 141, No. 18. pp. 3594-3604.
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