title: 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.
abstract: 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.
authors.affiliation: Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06032, USA.
authors.forename: Rachael P
authors.initials: RP
authors.lastname: Norris
authors.forename: Marina
authors.initials: M
authors.lastname: Freudzon
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mehlmann
authors.forename: Ann E
authors.initials: AE
authors.lastname: Cowan
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Simon
authors.forename: David L
authors.initials: DL
authors.lastname: Paul
authors.forename: Paul D
authors.initials: PD
authors.lastname: Lampe
authors.forename: Laurinda A
authors.initials: LA
authors.lastname: Jaffe
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D018031:Connexin 43 / Q000737:chemistry / Q000378:metabolism*; D054885:Cumulus Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008540:Meiosis / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000737:chemistry; D046509:Tissue Culture Techniques
chemical_list: D018031:Connexin 43; D012694:Serine; D007986:Luteinizing Hormone; D020929:Mitogen-Activated Protein Kinase Kinases
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