Sperm phospholipase Cζ from humans and cynomoigus monkeys triggers Ca2+ oscillations, activation and development of mouse oocytes

Sperm phospholipase Cζ from humans and cynomoigus monkeys triggers Ca2+ oscillations, activation and development of mouse oocytes
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DOI:
10.1530/rep.0.1240611
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发表时间:
2002-11-01
期刊:
影响因子:
3.8
通讯作者:
Lai, FA
Lai, FA
中科院分区:
生物学3区
文献类型:
--
作者:
Cox, LJ;Larman, MG;Lai, FA

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与受精精子的融合诱导哺乳动物卵母细胞在细胞质Ca2+中经历一系列显著的振荡,导致卵母细胞激活和胚胎发育。产生Ca2+振荡的确切分子机制尚未确定。在小鼠中发现了一种精子特异性磷脂酶C (PLC)的zeta亚型。小鼠PLC触发小鼠卵母细胞中的Ca2+振荡,并表现出与“精子因子”相同的特性,该因子已被提议在配子融合后扩散到卵母细胞中。本研究从人和食蟹猴的睾丸中分离出PLC同源物。与小鼠和猴子PLC蛋白序列的比较表明,人类PLCzeta的X-Y连接区域更短,并预测了明显不同的等电点。微量注射人类和食蟹猴PLC的互补RNA在小鼠卵母细胞中引起与小鼠受精期间相同的Ca2+振荡。此外,人PLCzeta诱导小鼠卵细胞激活和早期胚胎发育直至囊胚期,并且比来自猴子和小鼠的PLCzeta表现出更强的效力。这些结果与精子PLCzeta是受精过程中卵子激活的分子触发器的建议一致,并且PLCzeta的作用和活性在哺乳动物物种中高度保守。
Fusion with a fertilizing spermatozoon induces the mammalian oocyte to undergo a remarkable series of oscillations in cytosolic Ca2+, leading to oocyte activation and development of the embryo. The exact molecular mechanism for generating Ca2+ oscillations has not been established. A sperm-specific zeta isoform of phospholipase C (PLC.) has been identified in mice. Mouse PLC triggers Ca2+ oscillations in mouse oocytes and exhibits properties synonymous with the 'sperm factor' that has been proposed to diffuse into the oocyte after gamete fusion. The present study isolated the PLC homologue from human and cynomolgus monkey testes. Comparison with mouse and monkey PLC protein sequences indicates a shorter X-Y linker region in human PLCzeta and predicts a distinctly different isoelectric point. Microinjection of complementary RNA for both human and cynomolgus monkey PLC elicits Ca2+ oscillations in mouse oocytes equivalent to those seen during fertilization in mice. Moreover, human PLCzeta elicits mouse egg activation and early embryonic development up to the blastocyst stage, and exhibits greater potency than PLCzeta from monkeys and mice. These results are consistent with the proposal that sperm PLCzeta is the molecular trigger for egg activation during fertilization and that the role and activity of PLCzeta is highly conserved across mammalian species.