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 causes MAP kinase-dependent phosphorylation and closure of connexin 43 gap junctions in mouse ovarian follicles: one of two paths to meiotic resumption.
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DOI：
10.1242/dev.025494
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发表时间：
2008-10
期刊：
影响因子：
4.6
通讯作者：
Jaffe, Laurinda A.
中科院分区：
文献类型：
--
作者：
Norris, Rachael P.;Freudzon, Marina;Mehlmann, Lisa M.;Cowan, Ann E.;Simon, Alexander M.;Paul, David L.;Lampe, Paul D.;Jaffe, Laurinda A.
黄体生成素作用于卵泡，重新启动早期受阻的哺乳动物卵母细胞的减数分裂，这被认为是通过阻断减数分裂抑制信号而发生的，该信号通过缝隙连接从周围的体细胞传递到卵母细胞。为了研究这一想法，我们将荧光示踪剂显微注射到封闭有腔卵泡的活体小鼠卵母细胞中，并首次证明了在核膜破裂(NEBD)之前，黄体生成素导致体细胞之间的缝隙连接通透性降低。通透性的降低是由于丝氨酸255、262和279/282上连接蛋白43的MAP依赖的磷酸化所致。然后，我们测试了抑制缝隙连接通讯对于重新启动减数分裂是否充分和必要。降低缝隙连接通透性的抑制剂可引起NEBD，但阻断缝隙连接关闭的MAP激酶激活抑制剂不能预防NEBD。因此，MAP依赖的缝隙连接关闭和另一条冗余的途径同时发挥作用，以确保减数分裂在对黄体生成素的响应中恢复。
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 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 MAP kinase-dependent phosphorylation of connexin 43 on serines 255, 262, and 279/282. We then tested whether inhibition of gap junction communication is 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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