Understanding the molecular basis for sperm function: the sperm connecting piece and sperm motility

精子是一种运动细胞，它将父亲的遗传信息传递给卵母细胞。为了发挥功能，精子形态必须正常，精子必须具有运动性。通常，动物（和人类）男性不育与精子形态和功能异常有关。一种通常在无功能精子中观察到的表型是由“脆弱的”精子连接件引起的精子头部脱离。对养牛业来说，公牛的高生育力是重要的，而且具有经济效益。我们发现并鉴定了一种在动物物种中保守的由鸟氨酸脱羧酶抗酶3 Oaz3基因编码的精子蛋白p12。P12调节蛋白磷酸酶活性，这是精子运动的重要调节因子。在精子尾部p12可能调节精子尾部运动，但它也存在于连接部分。小鼠模型显示缺乏p12会导致连接片表型脆弱和尾巴运动异常。这种表型与牛工业的观察结果非常相似。我们建议研究p12如何参与精子尾部运动的调节和连接部分。我们将a)分析p12在连接片段中与哪些蛋白结合，b)分析p12是否调节连接片段蛋白的磷酸化，c) p12与Mypt3的关联对精子尾部磷酸酶活性和运动调节的重要性，d)使用特定p12突变蛋白的新型p12转基因小鼠模型分析p12在精子尾部运动中的功能。我们的实验将解决养牛业中的一个常见问题，并将为使用生殖技术诊断精子和优化程序的行业提供工具。

Spermatozoa are motile cells that transfer the father's genetic information to the oocyte. To function, sperm morphology must be normal, and sperm must acquire motility. Often, animal (and human) male infertility is related to abnormal sperm morphology and function. One phenotype, commonly observed for non-functional sperm, is sperm head detachment caused by a "fragile" sperm connecting piece. For cattle industry, high bull fertility is important and of economic consequence. We have discovered and characterized a sperm protein, p12 conserved among animal species, encoded by ornithine decarboxylase antizyme 3, Oaz3 gene. p12 modulates protein phosphatase activity, an important regulator of sperm motility. In sperm tails p12 likely regulates sperm tail motility but it is also present in the connecting piece. A mouse model shows that lack of p12 causes a fragile connecting piece phenotype and abnormal tail motility. This phenotype closely resembles observations made in the bovine industry.We propose to investigate how p12 is involved in regulation of sperm tail motility and in the connecting piece. We will a) analyze to which proteins p12 binds in the connecting piece, b) analyze if p12 regulates phosphorylation of connecting piece proteins, c) the importance of the association of p12 with Mypt3 on phosphatase activity in the sperm tail and regulation of motility, and d) analyze p12 function in sperm tail motility using novel transgenic mouse models for p12 using specific p12 mutant proteins.Our experiments will address a common problem in the cattle industry, and will provide tools to equip industry using reproductive technologies to diagnose sperm and optimize procedures.