Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 10 December 2004:
Vol. 306. no. 5703, pp. 1947 - 1950
DOI: 10.1126/science.1103974

Reports

The Gs-Linked Receptor GPR3 Maintains Meiotic Arrest in Mammalian Oocytes

Lisa M. Mehlmann,1* Yoshinaga Saeki,2{dagger} Shigeru Tanaka,2{dagger} Thomas J. Brennan,3{ddagger} Alexei V. Evsikov,4 Frank L. Pendola,4 Barbara B. Knowles,4 John J. Eppig,4 Laurinda A. Jaffe1*

Mammalian oocytes are held in prophase arrest by an unknown signal from the surrounding somatic cells. Here we show that the orphan Gs-linked receptor GPR3, which is localized in the oocyte, maintains this arrest. Oocytes from Gpr3 knockout mice resume meiosis within antral follicles, independently of an increase in luteinizing hormone, and this phenotype can be reversed by injection of Gpr3 RNA into the oocytes. Thus, the GPR3 receptor is a link in communication between the somatic cells and oocyte of the ovarian follicle and is crucial for the regulation of meiosis.

1 Department of Cell Biology, University of Connecticut Health Center (UCHC), Farmington, CT 06032, USA.
2 Massachusetts General Hospital, Charleston, MA 02129, USA.
3 Deltagen Inc., San Carlos, CA 94070, USA.
4 The Jackson Laboratory, Bar Harbor, ME 04609, USA.



{dagger} Present address: Ohio State University, Columbus, OH 43210, USA.

{ddagger} Present address: Toccata Therapeutics, Menlo Park, CA, 94025, USA.

* To whom correspondence should be addressed. E-mail: lmehlmann{at}neuron.uchc.edu (L.M.M.); ljaffe{at}neuron.uchc.edu (L.A.J.)

Read the Full Text



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Somatic cAMP signaling regulates MSP-dependent oocyte growth and meiotic maturation in C. elegans.
J. A. Govindan, S. Nadarajan, S. Kim, T. A. Starich, and D. Greenstein (2009)
Development 136, 2211-2221
   Abstract »    Full Text »    PDF »
Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte.
R. P. Norris, W. J. Ratzan, M. Freudzon, L. M. Mehlmann, J. Krall, M. A. Movsesian, H. Wang, H. Ke, V. O. Nikolaev, and L. A. Jaffe (2009)
Development 136, 1869-1878
   Abstract »    Full Text »    PDF »
Luteinizing hormone causes MAP kinase-dependent phosphorylation and closure of connexin 43 gap junctions in mouse ovarian follicles: one of two paths to meiotic resumption.
R. P. Norris, M. Freudzon, L. M. Mehlmann, A. E. Cowan, A. M. Simon, D. L. Paul, P. D. Lampe, and L. A. Jaffe (2008)
Development 135, 3229-3238
   Abstract »    Full Text »    PDF »
The Xenopus laevis Isoform of G Protein-Coupled Receptor 3 (GPR3) Is a Constitutively Active Cell Surface Receptor that Participates in Maintaining Meiotic Arrest in X. laevis Oocytes.
J. Deng, S. Lang, C. Wylie, and S. R. Hammes (2008)
Mol. Endocrinol. 22, 1853-1865
   Abstract »    Full Text »    PDF »
Estrogen Signaling Characteristics of Atlantic Croaker G Protein-Coupled Receptor 30 (GPR30) and Evidence It Is Involved in Maintenance of Oocyte Meiotic Arrest.
Y. Pang, J. Dong, and P. Thomas (2008)
Endocrinology 149, 3410-3426
   Abstract »    Full Text »    PDF »
Characterization of an Orphan G Protein-coupled Receptor, GPR20, That Constitutively Activates Gi Proteins.
M. Hase, T. Yokomizo, T. Shimizu, and M. Nakamura (2008)
J. Biol. Chem. 283, 12747-12755
   Abstract »    Full Text »    PDF »
Meiotic Arrest in Human Oocytes Is Maintained by a Gs Signaling Pathway.
A. DiLuigi, V. N. Weitzman, M. C. Pace, L. J. Siano, D. Maier, and L. M. Mehlmann (2008)
Biol Reprod 78, 667-672
   Abstract »    Full Text »    PDF »
Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age.
K. T. Jones (2008)
Hum. Reprod. Update 14, 143-158
   Abstract »    Full Text »    PDF »
Androgen Receptor Regulation of the Versican Gene through an Androgen Response Element in the Proximal Promoter.
J. T. Read, M. Rahmani, S. Boroomand, S. Allahverdian, B. M. McManus, and P. S. Rennie (2007)
J. Biol. Chem. 282, 31954-31963
   Abstract »    Full Text »    PDF »
Vesicular traffic at the cell membrane regulates oocyte meiotic arrest.
W. El-Jouni, S. Haun, R. Hodeify, A. Hosein Walker, and K. Machaca (2007)
Development 134, 3307-3315
   Abstract »    Full Text »    PDF »
Mechanisms Regulating Oocyte Meiotic Resumption: Roles of Mitogen-Activated Protein Kinase.
C.-G. Liang, Y.-Q. Su, H.-Y. Fan, H. Schatten, and Q.-Y. Sun (2007)
Mol. Endocrinol. 21, 2037-2055
   Abstract »    Full Text »    PDF »
Neural Expression of G Protein-coupled Receptors GPR3, GPR6, and GPR12 Up-regulates Cyclic AMP Levels and Promotes Neurite Outgrowth.
S. Tanaka, K. Ishii, K. Kasai, S. O. Yoon, and Y. Saeki (2007)
J. Biol. Chem. 282, 10506-10515
   Abstract »    Full Text »    PDF »
The Role of Xenopus Membrane Progesterone Receptor {beta} in Mediating the Effect of Progesterone on Oocyte Maturation.
L. Josefsberg Ben-Yehoshua, A. L. Lewellyn, P. Thomas, and J. L. Maller (2007)
Mol. Endocrinol. 21, 664-673
   Abstract »    Full Text »    PDF »
Luteinizing Hormone-Dependent Activation of the Epidermal Growth Factor Network Is Essential for Ovulation.
M. Hsieh, D. Lee, S. Panigone, K. Horner, R. Chen, A. Theologis, D. C. Lee, D. W. Threadgill, and M. Conti (2007)
Mol. Cell. Biol. 27, 1914-1924
   Abstract »    Full Text »    PDF »
Influence of follicular fluid meiosis-activating sterol on aneuploidy rate and precocious chromatid segregation in aged mouse oocytes.
S. Cukurcam, I. Betzendahl, G. Michel, E. Vogt, C. Hegele-Hartung, B. Lindenthal, and U. Eichenlaub-Ritter (2007)
Hum. Reprod. 22, 815-828
   Abstract »    Full Text »    PDF »
Meiotic Induction by Heat Stress in Mouse Oocytes: Involvement of AMP-Activated Protein Kinase and MAPK Family Members.
C. LaRosa and S. M. Downs (2007)
Biol Reprod 76, 476-486
   Abstract »    Full Text »    PDF »
Regulation of meiotic maturation.
F. J. Richard (2007)
J Anim Sci 85, E4-E6
   Abstract »    Full Text »    PDF »
PKA, Germ Cells, and Fertility.
K. A. Burton and G. S. McKnight (2007)
Physiology 22, 40-46
   Abstract »    Full Text »    PDF »
The CC genotype of the GNAS T393C polymorphism is associated with obesity and insulin resistance in women with polycystic ovary syndrome..
S. Hahn, U. H Frey, W. Siffert, S. Tan, K. Mann, and O. E Janssen (2006)
Eur. J. Endocrinol. 155, 763-770
   Abstract »    Full Text »    PDF »
Cracking the egg: molecular dynamics and evolutionary aspects of the transition from the fully grown oocyte to embryo.
A. V. Evsikov, J. H. Graber, J. M. Brockman, A. Hampl, A. E. Holbrook, P. Singh, J. J. Eppig, D. Solter, and B. B. Knowles (2006)
Genes & Dev. 20, 2713-2727
   Abstract »    Full Text »    PDF »
Ovarian follicle development and transgenic mouse models.
K.R. Barnett, C. Schilling, C.R. Greenfeld, D. Tomic, and J.A. Flaws (2006)
Hum. Reprod. Update 12, 537-555
   Abstract »    Full Text »    PDF »
An active protein kinase A (PKA) is involved in meiotic arrest of rat growing oocytes.
M. Kovo, M. Kandli-Cohen, M. Ben-Haim, D. Galiani, D. W Carr, and N. Dekel (2006)
Reproduction 132, 33-43
   Abstract »    Full Text »    PDF »
Disruption of Gap Junctional Communication within the Ovarian Follicle Induces Oocyte Maturation.
S. Sela-Abramovich, I. Edry, D. Galiani, N. Nevo, and N. Dekel (2006)
Endocrinology 147, 2280-2286
   Abstract »    Full Text »    PDF »
Role of the Epidermal Growth Factor Network in Ovarian Follicles.
M. Conti, M. Hsieh, J.-Y. Park, and Y.-Q. Su (2006)
Mol. Endocrinol. 20, 715-723
   Abstract »    Full Text »    PDF »
N-cadherin mediated cell contact inhibits germinal vesicle breakdown in mouse oocytes maintained in vitro..
J J Peluso (2006)
Reproduction 131, 429-437
   Abstract »    Full Text »    PDF »
Calcium at Fertilization and in Early Development.
M. Whitaker (2006)
Physiol Rev 86, 25-88
   Abstract »    Full Text »    PDF »
Focus on Meiosis.
M. Herbert (2005)
Reproduction 130, 759-760
   Full Text »    PDF »
Stops and starts in mammalian oocytes: recent advances in understanding the regulation of meiotic arrest and oocyte maturation.
L. M Mehlmann (2005)
Reproduction 130, 791-799
   Abstract »    Full Text »    PDF »
Epidermal growth factor receptor signaling is required for normal ovarian steroidogenesis and oocyte maturation.
M. Jamnongjit, A. Gill, and S. R. Hammes (2005)
PNAS 102, 16257-16262
   Abstract »    Full Text »    PDF »
Regulation of meiotic prophase arrest in mouse oocytes by GPR3, a constitutive activator of the Gs G protein.
L. Freudzon, R. P. Norris, A. R. Hand, S. Tanaka, Y. Saeki, T. L.Z. Jones, M. M. Rasenick, C. H. Berlot, L. M. Mehlmann, and L. A. Jaffe (2005)
J. Cell Biol. 171, 255-265
   Abstract »    Full Text »    PDF »
Mammalian G Proteins and Their Cell Type Specific Functions.
N. Wettschureck and S. Offermanns (2005)
Physiol Rev 85, 1159-1204
   Abstract »    Full Text »    PDF »
Cyclic Adenosine 3',5'-Monophosphate-Dependent Activation of Mitogen-Activated Protein Kinase in Cumulus Cells Is Essential for Germinal Vesicle Breakdown of Porcine Cumulus-Enclosed Oocytes.
C.-G. Liang, L.-J. Huo, Z.-S. Zhong, D.-Y. Chen, H. Schatten, and Q.-Y. Sun (2005)
Endocrinology 146, 4437-4444
   Abstract »    Full Text »    PDF »
Serotonin and Its Antidepressant-Sensitive Transport in Mouse Cumulus-Oocyte Complexes and Early Embryos.
P. Amireault and F. Dube (2005)
Biol Reprod 73, 358-365
   Abstract »    Full Text »    PDF »
Regulation of the G2/M Transition in Xenopus Oocytes by the cAMP-dependent Protein Kinase.
P. A. Eyers, J. Liu, N. R. Hayashi, A. L. Lewellyn, J. Gautier, and J. L. Maller (2005)
J. Biol. Chem. 280, 24339-24346
   Abstract »    Full Text »    PDF »
Premature ovarian aging in mice deficient for Gpr3.
C. Ledent, I. Demeestere, D. Blum, J. Petermans, T. Hamalainen, G. Smits, and G. Vassart (2005)
PNAS 102, 8922-8926
   Abstract »    Full Text »    PDF »
Before Their Time.
R. J. Davenport (2005)
Sci. Aging Knowl. Environ. 2005, nf44
   Abstract »    Full Text »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)