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First published online September 5, 2008
doi: 10.1242/10.1242/dev.025494


Development 135, 3229-3238 (2008)
Published by The Company of Biologists 2008


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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

Rachael P. Norris1,*, Marina Freudzon1,*, Lisa M. Mehlmann1, Ann E. Cowan2, Alexander M. Simon3, David L. Paul4, Paul D. Lampe5,{dagger} and Laurinda A. Jaffe1,{dagger}

1 Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06032, USA.
2 Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT 06032, USA.
3 Department of Physiology, University of Arizona School of Medicine, Tucson, AZ 85724, USA.
4 Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
5 Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

{dagger} Authors for correspondence (e-mails: plampe{at}fhcrc.org; ljaffe{at}neuron.uchc.edu)

Accepted 8 August 2008

Luteinizing hormone (LH) acts on ovarian follicles to reinitiate meiosis in prophase-arrested mammalian oocytes, and this has been proposed to occur by interruption of a meioisis-inhibitory signal that is transmitted through gap junctions into the oocyte from the somatic cells that surround it. To investigate this idea, we microinjected fluorescent tracers into live antral follicle-enclosed mouse oocytes, and we demonstrate for the first time that LH causes a decrease in the gap junction permeability between the somatic cells, prior to nuclear envelope breakdown (NEBD). The decreased permeability results from the MAP kinase-dependent phosphorylation of connexin 43 on serines 255, 262 and 279/282. We then tested whether the inhibition of gap junction communication was sufficient and necessary for the reinitiation of meiosis. Inhibitors that reduced gap junction permeability caused NEBD, but an inhibitor of MAP kinase activation that blocked gap junction closure in response to LH did not prevent NEBD. Thus, both MAP kinase-dependent gap junction closure and another redundant pathway function in parallel to ensure that meiosis resumes in response to LH.


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Development 2008 135: e1905. [Full Text]  



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