Ca2+ influx and the store-operated Ca2+ entry pathway undergo regulation during mouse oocyte maturation.
Ca2+ influx and the store-operated Ca2+ entry pathway undergo regulation during mouse oocyte maturation.
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DOI：
10.1091/mbc.e13-01-0065
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发表时间：
2013-05
影响因子：
3.3
通讯作者：
Fissore RA
中科院分区：
文献类型：
--
作者：
Cheon B;Lee HC;Wakai T;Fissore RA
Ca2+稳态的变化使卵母细胞能够经历[Ca2+]i振荡和激活。在小鼠卵母细胞成熟过程中，Ca2+内流和SOCE下调，而[Ca2+]ER含量增加。绕过Ca2+内流的下调会干扰卵母细胞成熟。在准备受精时，哺乳动物卵母细胞经历调节钙稳态机制的优化。这些变化包括Ca2+储存（[Ca2+]ER）含量的增加，这一过程需要Ca2+内流。尽管如此，介导这种内流的机制仍然不清楚，尽管已知[Ca2+]ER可以通过储存操作的Ca2+进入（SOCE）调节Ca2+内流。我们发现在成熟过程中，随着[Ca2+]ER的增加，Ca2+内流减少。我们证明，小鼠卵母细胞/卵子表达sce -基质相互作用分子1 （Stim1）和orai1的两种分子成分，人类(h) Stim1的表达以一种概括内源性SOCE的方式增加Ca2+内流。我们观察到成熟过程中hStim1和hOrai1的细胞分布经历了彻底的变化，从而减少了它们在成熟后期的共定位。hStim1和hOrai1的共表达增强了成熟过程中的内流，但仅在GV卵母细胞中增加了基础Ca2+水平。此外，hStim1 + Orai1的组成型活性形式的表达，在成熟过程中增加基础Ca2+，干扰减数分裂的恢复。综上所述，我们的研究结果表明，Ca2+内流和SOCE在成熟过程中受到调节，Ca2+稳态的改变破坏了小鼠卵母细胞的成熟。
Changes in Ca2+ homeostasis render oocytes competent to undergo [Ca2+]i oscillations and activation. During mouse oocyte maturation Ca2+ influx and SOCE are down-regulated, whereas [Ca2+]ER content increases. Bypassing the down-regulation of Ca2+ influx disturbs oocyte maturation. In preparation for fertilization, mammalian oocytes undergo optimization of the mechanisms that regulate calcium homeostasis. Among these changes is the increase in the content of the Ca2+ stores ([Ca2+]ER), a process that requires Ca2+ influx. Nevertheless, the mechanism(s) that mediates this influx remains obscure, although is known that [Ca2+]ER can regulate Ca2+ influx via store-operated Ca2+ entry (SOCE). We find that during maturation, as [Ca2+]ER increases, Ca2+ influx decreases. We demonstrate that mouse oocytes/eggs express the two molecular components of SOCE—stromal interaction molecule 1 (Stim1) and Orai1—and expression of human (h) Stim1 increases Ca2+ influx in a manner that recapitulates endogenous SOCE. We observe that the cellular distribution of hStim1 and hOrai1 during maturation undergoes sweeping changes that curtail their colocalization during the later stages of maturation. Coexpression of hStim1 and hOrai1 enhances influx throughout maturation but increases basal Ca2+ levels only in GV oocytes. Further, expression of a constitutive active form of hStim1 plus Orai1, which increases basal Ca2+ throughout maturation, disturbs resumption of meiosis. Taken together, our results demonstrate that Ca2+ influx and SOCE are regulated during maturation and that alteration of Ca2+ homeostasis undermines maturation in mouse oocytes.