Protein phosphatase PP1γ2 in sperm morphogenesis and epididymal initiation of sperm motility

Protein phosphatase PP1γ2 in sperm morphogenesis and epididymal initiation of sperm motility
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DOI:
10.1111/j.1745-7262.2007.00307.x
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发表时间:
2007-07-01
影响因子:
2.9
通讯作者:
Vijayaraghavan, Srinivasan
Vijayaraghavan, Srinivasan
中科院分区:
医学2区
文献类型:
--
作者:
Chakrabarti, Rumela;Cheng, Lina;Vijayaraghavan, Srinivasan

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丝氨酸/苏氨酸磷酸酶(PP 1)亚型PP 1 γ 2主要在睾丸中表达,是精子中的关键酶。高PP 1 γ 2催化活性在未成熟精子中保持运动性。PP 1 γ 2的抑制导致未成熟精子的运动启动和成熟精子的运动刺激和鞭毛搏动参数的变化。PP 1 γ 2亚型存在于所有研究的哺乳动物精子中:小鼠,大鼠,仓鼠,牛,非人灵长类动物和人。我们现在已经确定了至少四个其调节蛋白,调节不同的池内的PP 1 γ 2精子。我们的研究提供了新的见解生化机制的发展和调节精子活力。我们假设,作为磷酸化和可逆结合的调节蛋白的催化亚基的结果,在精子PP 1 γ 2活性的变化是至关重要的发展和调节的运动和精子受精卵的能力。有针对性地破坏编码PP 1 γ 1或PP 1 γ 2亚型的Ppp 1cc基因,会导致小鼠精子生成受损导致雄性不育。我们的观察结果表明,除了运动,蛋白磷酸酶PP 1 γ 2可能发挥异构体的特定功能,在专门的鞭毛结构的哺乳动物精子的发展。
The serine/threonine phosphatase (PP1) isoform PP1 gamma 2, predominantly expressed in the testis, is a key enzyme in spermatozoa. High PP1 gamma 2 catalytic activity holds motility in check in immature spermatozoa. Inhibition of PP1 gamma 2 causes motility initiation in immature spermatozoa and motility stimulation and changes in flagellar beat parameters in mature spermatozoa. The PP1 gamma 2 isoform is present in all mammalian spermatozoa studied: mouse, rat, hamster, bovine, non-human primate and man. We have now identified at least four of its regulatory proteins that regulate distinct pools of PP1 gamma 2 within spermatozoa. Our studies provide new ' insights into biochemical mechanisms underlying development and regulation of sperm motility. We hypothesize that changes in sperm PP1 gamma 2 activity as a result of phosphorylation and reversible binding of the regulatory proteins to the catalytic subunit are critical in the development and regulation of motility and the ability of sperm to fertilize eggs. Targeted disruption of the Ppp1cc gene, which encodes the PP1 gamma 1 or PP1 gamma 2 isoforms, causes male infertility in mice as a result of impaired spermiogenesis. Our observations suggest that, in addition to motility, the protein phosphatase PP1 gamma 2 might play an isoform-specific function in the development of specialized flagellar structures of mammalian spermatozoa.