Exploring sperm function

射精时，精子不能受精。 它们必须首先经历获能，获能被广义地定义为使精子能够受精的修饰。获能的一个标志是精子能够进行顶体反应，这是一种钙依赖性的分泌事件，响应于卵子的细胞外基质，透明质酸。精子是一种高度区室化和非转录的细胞，如何经历复杂的获能和顶体反应仍不清楚。使用猪模型，我们以前表明，获能与“p32”，酪氨酸磷蛋白的外观。早期的蛋白质组学揭示，p32实际上是>9个酪氨酸磷蛋白的复合物，并且在获能期间出现的主要酪氨酸磷蛋白是Sp32。该蛋白最初被认为是参与顶体蛋白成熟的顶体蛋白，然而，Sp32本身具有透明带结合亲和力，并已被鉴定为癌症-睾丸抗原。我们的长期目标是在比较生物学的背景下，建立一个完整的模型，精子功能的基因和蛋白质水平，包括获能和顶体反应。我们的短期目标是确定，本地化和p32复合物的组成部分，以p32和识别介导的获能和顶体反应的途径。本课程将阐明翻译后蛋白质修饰如何导致精子的能力，以及获能和顶体反应是如何调节的。这种以使用为灵感的基础研究有助于解决不孕症的原因，制定合理的避孕措施，改善辅助生殖技术，并解释对男性生殖的毒理学影响。生育控制在人类和兽医学、畜牧业、害虫控制以及保护濒危物种方面都是必要的。

At ejaculation, sperm cannot fertilise. They must first undergo capacitation, which is broadly defined as the modifications that render sperm competent to fertilise. A hallmark of capacitation is the ability of the sperm to undergo the acrosome reaction, a calcium-dependent, secretory event, in response to the egg's extracellular matrix, the zona pellucida. Just how the sperm, a highly compartmentalised and non-transcriptional cell, undergoes the complexities of capacitation and the acrosome reaction remains unclear. Using the porcine model, we previously showed that capacitation is associated with the appearance of "p32", a tyrosine phosphoprotein. Early proteomics revealed that p32 is actually a complex of >9 tyrosine phosphoproteins and that the principle tyrosine phosphoprotein appearing during capacitation to be Sp32. This protein was first known as an acrosomal protein involved in acrosin maturation, however, Sp32 itself has zona-binding affinity and has been identified as a cancer-testis antigen. Our long term objective is to establish an integrated model of sperm function at the gene and protein level including capacitation and the acrosome reaction in a context of comparative biology. Our short term objectives are to identify, localise and characterise p32 complex components, to characterise Sp32 and to identify the pathways mediating capacitation and the acrosome reaction. This program will clarify how post-translational protein modifications lead to sperm competence and how capacitation and the acrosome reaction are regulated. Such use-inspired basic research is instrumental to resolve causes of infertility, formulate rational contraception, improve assisted reproductive techniques, and interpret toxicological effects on male reproduction. Fertility control is necessary in human and veterinary medicine, animal agriculture, pest control, and to conserve endangered species.