Identification and characterization of two distinct PPP1R2 isoforms in human spermatozoa.
Identification and characterization of two distinct PPP1R2 isoforms in human spermatozoa.
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DOI：
10.1186/1471-2121-14-15
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发表时间：
2013-03-18
期刊：
影响因子：
--
通讯作者：
da Cruz E Silva EF
中科院分区：
文献类型：
--
作者：
Korrodi-Gregório L;Ferreira M;Vintém AP;Wu W;Muller T;Marcus K;Vijayaraghavan S;Brautigan DL;da Cruz E Silva OA;Fardilha M;da Cruz E Silva EF
蛋白丝/苏氨酸磷酸酶 PPP1CC2 是 PPP1C 的选择性剪接亚型，在睾丸中高度富集并在精子中选择性表达。将磷酸酶抑制剂毒素冈田酸或花萼蛋白 A 添加到头部和尾部精子中，分别触发和刺激精子活力。因此，磷酸酶抑制的内源机制是控制精子功能的基础，应该对其进行表征。初步结果显示，牛和灵长类精子中的蛋白磷酸酶抑制剂活性类似于 PPP1R2。在这里，我们首次明确表明 PPP1R2 存在于精子中。此外，我们还鉴定了一种新的蛋白质，PPP1R2P3。后者以前被认为是无内含子的假基因。我们表明与假基因相对应的蛋白质被表达。它具有与 PPP1R2 相似的 PPP1 抑制效力。 PPP1R2 中的潜在磷酸位点被 PPP1R2P3 中的不可磷酸化残基 T73P 和 S87R 取代。我们还确认 PPP1R2/PPP1R2P3 在 Ser121 和 Ser122 处被磷酸化，并报告了一个新的磷酸化位点 Ser127。精子结构细分显示PPP1CC2、PPP1R2/PPP1R2P3位于头部和尾部结构。精子PPP1R2和PPP1R2P3的最终鉴定和定位为未来研究它们在顶体反应、精子活力和过度激活中的作用奠定了基础。一个有趣的可能性是，PPP1CC2 抑制亚基的转换可能会触发附睾中的精子活力和/或女性生殖道中的精子过度活跃。
Protein Ser/Thr Phosphatase PPP1CC2 is an alternatively spliced isoform of PPP1C that is highly enriched in testis and selectively expressed in sperm. Addition of the phosphatase inhibitor toxins okadaic acid or calyculin A to caput and caudal sperm triggers and stimulates motility, respectively. Thus, the endogenous mechanisms of phosphatase inhibition are fundamental for controlling sperm function and should be characterized. Preliminary results have shown a protein phosphatase inhibitor activity resembling PPP1R2 in bovine and primate spermatozoa. Here we show conclusively, for the first time, that PPP1R2 is present in sperm. In addition, we have also identified a novel protein, PPP1R2P3. The latter was previously thought to be an intron-less pseudogene. We show that the protein corresponding to the pseudogene is expressed. It has PPP1 inhibitory potency similar to PPP1R2. The potential phosphosites in PPP1R2 are substituted by non-phosphorylable residues, T73P and S87R, in PPP1R2P3. We also confirm that PPP1R2/PPP1R2P3 are phosphorylated at Ser121 and Ser122, and report a novel phosphorylation site, Ser127. Subfractionation of sperm structures show that PPP1CC2, PPP1R2/PPP1R2P3 are located in the head and tail structures. The conclusive identification and localization of sperm PPP1R2 and PPP1R2P3 lays the basis for future studies on their roles in acrosome reaction, sperm motility and hyperactivation. An intriguing possibility is that a switch in PPP1CC2 inhibitory subunits could be the trigger for sperm motility in the epididymis and/or sperm hyperactivation in the female reproductive tract.
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影响因子：
4.8
作者：
Hurley, Thomas D.;Yang, Jie;DePaoli-Roach, Anna A.
通讯作者：
DePaoli-Roach, Anna A.
影响因子：
2.9
作者：
Chakrabarti, Rumela;Cheng, Lina;Vijayaraghavan, Srinivasan
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影响因子：
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作者：
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通讯作者：
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作者：
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通讯作者：
Choo, Kong-Bung
影响因子：
3.5
作者：
ASHIZAWA, K;WISHART, GJ;TSUZUKI, Y
通讯作者：
TSUZUKI, Y