TRPM7-like channels are functionally expressed in oocytes and modulate post-fertilization embryo development in mouse.

TRPM7-like channels are functionally expressed in oocytes and modulate post-fertilization embryo development in mouse.
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DOI:
10.1038/srep34236
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发表时间:
2016-09-29
期刊:
影响因子:
4.6
通讯作者:
Lykke-Hartmann K
Lykke-Hartmann K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Carvacho I;Ardestani G;Lee HC;McGarvey K;Fissore RA;Lykke-Hartmann K

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瞬时受体电位(TRP)通道是一类广泛存在于哺乳动物组织中的阳离子通道。一般而言,个体TRP通道的整体遗传破坏导致与特定组织和/或器官功能受损相关的表型。一个例外是TRP通道TRPM 7的遗传消融,其导致早期胚胎致死。然而,TRPM 7在卵母细胞、卵子和植入前胚胎中的功能仍然未知。在这里,我们描述了一个外向整流非选择性电流介导的TRP离子通道在未成熟卵母细胞(萌发囊泡阶段),成熟卵母细胞(中期II鸡蛋)和2-细胞期胚胎。该电流被特异性激动剂激活,并被与TRPM 7通道的功能表达一致的不同阻断剂抑制。我们证明了TRPM 7样通道是同源四聚体,它们的激活介导卵母细胞和卵子中的钙内流,这是支持受精和卵子激活的基础。最后,我们发现,通道功能的药理学抑制延迟植入前胚胎发育,并减少向胚泡阶段的进展。我们的数据表明TRPM 7样通道在小鼠卵母细胞,卵子和胚胎中的功能表达,可能在胚胎发育的启动中发挥重要作用。
The Transient Receptor Potential (TRP) channels are a family of cationic ion channels widely distributed in mammalian tissues. In general, the global genetic disruption of individual TRP channels result in phenotypes associated with impairment of a particular tissue and/or organ function. An exception is the genetic ablation of the TRP channel TRPM7, which results in early embryonic lethality. Nevertheless, the function of TRPM7 in oocytes, eggs and pre-implantation embryos remains unknown. Here, we described an outward rectifying non-selective current mediated by a TRP ion channel in immature oocytes (germinal vesicle stage), matured oocytes (metaphase II eggs) and 2-cell stage embryos. The current is activated by specific agonists and inhibited by distinct blockers consistent with the functional expression of TRPM7 channels. We demonstrated that the TRPM7-like channels are homo-tetramers and their activation mediates calcium influx in oocytes and eggs, which is fundamental to support fertilization and egg activation. Lastly, we showed that pharmacological inhibition of the channel function delays pre-implantation embryo development and reduces progression to the blastocyst stage. Our data demonstrate functional expression of TRPM7-like channels in mouse oocytes, eggs and embryos that may play an essential role in the initiation of embryo development.
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