title: Regulator of G-protein signaling 2 (RGS2) suppresses premature calcium release in mouse eggs.
abstract: During oocyte maturation, capacity and sensitivity of Ca(2+) signaling machinery increases dramatically, preparing the metaphase II (MII)-arrested egg for fertilization. Upon sperm-egg fusion, Ca(2+) release from IP3-sensitive endoplasmic reticulum stores results in cytoplasmic Ca(2+) oscillations that drive egg activation and initiate early embryo development. Premature Ca(2+) release can cause parthenogenetic activation prior to fertilization; thus, preventing inappropriate Ca(2+) signaling is crucial for ensuring robust MII arrest. Here, we show that regulator of G-protein signaling 2 (RGS2) suppresses Ca(2+) release in MII eggs. Rgs2 mRNA was recruited for translation during oocyte maturation, resulting in ∼ 20-fold more RGS2 protein in MII eggs than in fully grown immature oocytes. Rgs2-siRNA-injected oocytes matured to MII; however, they had increased sensitivity to low pH and acetylcholine (ACh), which caused inappropriate Ca(2+) release and premature egg activation. When matured in vitro, RGS2-depleted eggs underwent spontaneous Ca(2+) increases that were sufficient to cause premature zona pellucida conversion. Rgs2(-/-) females had reduced litter sizes, and their eggs had increased sensitivity to low pH and ACh. Rgs2(-/-) eggs also underwent premature zona pellucida conversion in vivo. These findings indicate that RGS2 functions as a brake to suppress premature Ca(2+) release in eggs that are poised on the brink of development.
authors.affiliation: Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Miranda L
authors.initials: ML
authors.lastname: Bernhardt
authors.affiliation: Department of Cell Biology, UConn Health, Farmington, CT 06030, USA.
authors.forename: Katie M
authors.initials: KM
authors.lastname: Lowther
authors.affiliation: Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Padilla-Banks
authors.affiliation: Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: McDonough
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.
authors.forename: Katherine N
authors.initials: KN
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA.
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Evsikov
authors.affiliation: Department of Cell Biology, UConn Health, Farmington, CT 06030, USA.
authors.forename: Tracy F
authors.initials: TF
authors.lastname: Uliasz
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.
authors.forename: Peter
authors.initials: P
authors.lastname: Chidiac
authors.affiliation: Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA williamsc5@niehs.nih.gov lmehlman@uchc.edu.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Williams
authors.affiliation: Department of Cell Biology, UConn Health, Farmington, CT 06030, USA williamsc5@niehs.nih.gov lmehlman@uchc.edu.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mehlmann
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D051379:Mice; D010063:Ovum / Q000378:metabolism / Q000502:physiology*; D020710:RGS Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013084:Sperm-Ovum Interactions / Q000502:physiology*; D018709:Statistics, Nonparametric
chemical_list: D020710:RGS Proteins; C105345:Rgs2 protein, mouse; D002118:Calcium
keywords: Calcium; Egg activation; Gq; Meiotic maturation; Oocyte; RGS2