Gβγ signaling reduces intracellular cAMP to promote meiotic progression in mouse oocytes
Gβγ signaling reduces intracellular cAMP to promote meiotic progression in mouse oocytes
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DOI：
10.1016/j.steroids.2006.11.006
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发表时间：
2007-02-01
期刊：
影响因子：
2.7
通讯作者：
Hammes, Stephen R.
中科院分区：
文献类型：
--
作者：
Gill, Arvind;Hammes, Stephen R.
几乎在每一种脊椎动物中，升高的胞内cAMP维持卵母细胞处于减数分裂的前期I。在排卵之前，促性腺激素触发各种卵巢内过程，包括间隙连接的破坏，EGF受体的激活和类固醇的分泌。这些事件反过来又降低了选定卵母细胞中的细胞内cAMP水平，以允许减数分裂进程或成熟恢复。研究表明，cAMP水平保持在休眠卵母细胞的组成性G蛋白信号升高，并在细胞内cAMP的下降，伴随成熟可能是由于这种抑制性G蛋白介导的信号衰减的一部分。有趣的是，减数分裂停滞的这些G蛋白调节剂之一是G α（s）蛋白，其刺激腺苷酸环化酶以提高卵母细胞发育的两个重要动物模型中的细胞内cAMP：非洲爪蟾青蛙和小鼠。除了G α（s），组成性G β γ活性类似地刺激腺苷酸环化酶，以提高cAMP和防止非洲爪蟾卵母细胞的成熟;然而，G β γ在调节小鼠卵母细胞减数分裂中的作用尚未得到研究。在这里，我们表明，G β γ并不有助于维持小鼠卵母细胞减数分裂停滞。事实上，与青蛙卵母细胞中的观察相反，小鼠卵母细胞中的G β γ信号降低cAMP并促进卵母细胞成熟，这表明G β γ实际上可能在促进卵母细胞成熟中发挥积极作用。这些观察结果强调，虽然许多一般概念和减数分裂调控的组成部分是保守的从青蛙到小鼠，具体的差异存在，可能会导致重要的见解，在脊椎动物的卵巢发育。(c)2006爱思唯尔公司All rights reserved.
in nearly every vertebrate species, elevated intracellular cAMP maintains oocytes in prophase I of meiosis. Prior to ovulation, gonadotropins trigger various intra-ovarian processes, including the breakdown of gap junctions, the activation of EGF receptors, and the secretion of steroids. These events in turn decrease intracellular cAMP levels in select oocytes to allow meiotic progression, or maturation, to resume. Studies suggest that cAMP levels are kept elevated in resting oocytes by constitutive G protein signaling, and that the drop in intracellular cAMP that accompanies maturation may be due in part to attenuation of this inhibitory G protein-mediated signaling. Interestingly, one of these G protein regulators of meiotic arrest is the G alpha(s) protein, which stimulates adenylyl cyclase to raise intracellular cAMP in two important animal models of oocyte development: Xenopus leavis frogs and mice. In addition to G alpha(s), constitutive G beta gamma activity similarly stimulates adenylyl cyclase to raise cAMP and prevent maturation in Xenopus oocytes; however, the role of G beta gamma in regulating meiosis in mouse oocytes has not been examined. Here we show that G beta gamma does not contribute to the maintenance of murine oocyte meiotic arrest. In fact, contrary to observations in frog oocytes, G beta gamma signaling in mouse oocytes reduces cAMP and promotes oocyte maturation, suggesting that G beta gamma might in fact play a positive role in promoting oocyte maturation. These observations emphasize that, while many general concepts and components of meiotic regulation are conserved from frogs to mice, specific differences exist that may lead to important insights regarding ovarian development in vertebrates. (c) 2006 Elsevier Inc. All rights reserved.