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.
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.
Norris
Rachael P
RP
Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06032, USA.
Freudzon
Marina
M
Mehlmann
Lisa M
LM
Cowan
Ann E
AE
Simon
Alexander M
AM
Paul
David L
DL
Lampe
Paul D
PD
Jaffe
Laurinda A
LA
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
D018031:Connexin 43; D012694:Serine; D007986:Luteinizing Hormone; D020929:Mitogen-Activated Protein Kinase Kinases
J Biol Chem. 2002 Nov 22;277(47):44962-8
12270943
Dev Biol. 2008 May 1;317(1):380-8
18381211
Mol Biol Cell. 2003 May;14(5):1808-17
12802057
Reproduction. 2005 Dec;130(6):791-9
16322539
Dev Biol. 1985 Mar;108(1):191-202
3972175
Biol Reprod. 2007 Jul;77(1):2-8
17314311
Immunol Today. 1999 Jun;20(6):254-7
10354549
Biophys J. 2004 Aug;87(2):958-73
15298902
J Exp Med. 1935 Oct 31;62(5):665-75
19870440
Endocrinology. 2005 Mar;146(3):1236-44
15576461
Dev Dyn. 1994 May;200(1):1-13
8081010
Methods Mol Biol. 2001;154:447-76
11218664
J Cell Sci. 2007 Dec 1;120(Pt 23):4117-25
18032785
Dev Biol. 1989 Aug;134(2):297-306
2744234
J Cell Biol. 1995 Jul;130(2):275-84
7615631
Hum Reprod. 1991 Mar;6(3):411-22
1659586
Dev Biol. 2007 Oct 15;310(2):240-9
17850783
Dev Biol. 1982 Jan;89(1):268-72
7054011
Reproduction. 2007 Mar;133(3):641-51
17379658
Dev Biol. 2003 Nov 1;263(1):126-38
14568551
Circ Res. 1999 Jun 25;84(12):1365-79
10381888
J Cell Biol. 2007 Dec 17;179(6):1301-9
18086922
Reproduction. 2002 May;123(5):613-20
12006089
Endocrinology. 2004 Apr;145(4):1617-24
14684606
Dev Cell. 2005 Mar;8(3):401-11
15737935
Biol Reprod. 2008 Apr;78(4):667-72
18184921
J Cell Biol. 2005 Oct 24;171(2):255-65
16247026
Science. 2002 Aug 23;297(5585):1343-5
12193786
Biol Reprod. 1991 Dec;45(6):824-30
1666849
J Biol Chem. 1994 Dec 2;269(48):30502-9
7982967
Methods Cell Biol. 2004;74:219-42
15575609
J Cell Biol. 1978 Jul;78(1):58-75
670298
Dev Biol. 2004 Mar 1;267(1):1-13
14975713
Acta Physiol Scand. 1990 Jul;139(3):511-7
2173353
J Biol Chem. 1998 Jul 17;273(29):18623-32
9660836
Nat Methods. 2005 Dec;2(12):932-40
16299478
Endocrinology. 2006 May;147(5):2280-6
16439460
Mol Reprod Dev. 2008 Jan;75(1):105-14
17549700
Dev Biol. 2003 Jun 15;258(2):385-96
12798295
Biol Reprod. 1987 Mar;36(2):431-7
2883997
Cell Regul. 1990 Dec;1(13):989-1002
1966893
Cell Commun Adhes. 2008 May;15(1):75-84
18649180
Hum Reprod Update. 2008 Mar-Apr;14(2):143-58
18084010
J Exp Zool. 1988 Jan;245(1):86-96
2832512
J Cell Sci. 2004 Jan 26;117(Pt 3):507-14
14702389
Proc Natl Acad Sci U S A. 2005 Jun 21;102(25):8922-6
15956199
J Cell Biol. 2001 Aug 20;154(4):815-27
11514593
J Clin Invest. 2004 Jul;114(2):196-205
15254586
J Biol Chem. 1996 Feb 16;271(7):3779-86
8631994
J Cell Sci. 2005 Nov 1;118(Pt 21):5071-8
16254245
J Biol Chem. 2005 Nov 25;280(47):39168-74
16172121
Biochem J. 2006 Mar 15;394(Pt 3):527-43
16492141
Science. 2004 Dec 10;306(5703):1947-50
15591206
Dev Biol. 1983 Jun;97(2):264-73
6189752
Endocrinology. 2002 Jun;143(6):2221-32
12021186
J Biol Chem. 1998 Apr 10;273(15):9188-96
9535909
Am J Physiol Cell Physiol. 2006 Jan;290(1):C290-7
16135542
Biol Reprod. 1981 Dec;25(5):1119-34
7326302
Mol Endocrinol. 2008 Apr;22(4):924-36
18187604
Dev Biol. 2005 Dec 15;288(2):397-404
16289135
Dev Biol. 1987 Jul;122(1):61-71
3596012
EMBO Rep. 2006 Mar;7(3):321-5
16374506
Biochem J. 2007 Dec 15;408(3):375-85
17714073
Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8420-7
9671692
J Reprod Fertil. 1996 Jul;107(2):255-64
8882293
Nature. 1997 Feb 6;385(6616):525-9
9020357
J Morphol. 1978 Jun;156(3):339-66
671553
J Cell Sci. 2006 Aug 15;119(Pt 16):3435-42
16882687
Nature. 1965 Oct 23;208(5008):349-51
4957259
J Cell Biol. 2000 Jun 26;149(7):1503-12
10871288
Dev Biol. 2005 Nov 15;287(2):249-61
16229830
J Cell Biol. 1989 Feb;108(2):595-605
2537319
Cell Commun Adhes. 2006 Jan-Apr;13(1-2):61-77
16613781
J Cell Sci. 2004 Jun 1;117(Pt 13):2699-707
15138288
Biol Reprod. 2008 Jun;78(6):1111-8
18337515
Methods Mol Biol. 2009;518:157-73
19085139