Studies on the Eppin family of proteins on chromosome 20

描述（由申请人提供）：本研究项目的长期目标是了解Eppin的功能：它与精子表面分子复合物中结合伙伴的相互作用，它与前列腺特异性抗原（PSA）的关系，以及它在射精后恢复精子活力中的作用。人类射精后精子表面蛋白质-蛋白质相互作用的分子细节所知甚少，而此时恢复完全的运动能力对生育能力至关重要。作为在这一关键阶段理解男性配子生物学的一种新方法，修订后的研究计划将寻求理解Eppin与其结合伴侣及其受体在人类精子表面的相互作用，特别是关于射精后精子活力的恢复。具体目标#1将描述在人类精子表面发现的Eppin蛋白复合物。epin和semenogelin与另外两种表面蛋白，即聚簇蛋白和乳铁蛋白相关。因此，在这个项目的发现阶段，具体目标#1将详细描述这个复合物，并测试我们的假设，即抗Eppin抗体会破坏Eppin蛋白复合物。具体目标#2将识别和表征精子上的Eppin和目标#1中描述的Eppin蛋白复合物的受体。我们的假设是，Eppin及其复合体有一个或多个精子受体，它们的身份将有助于更好地了解Eppin在复合体中的功能。特异性目的#3将描述人类前列腺特异性抗原(PSA)-Eppin相互作用及其对精子运动的影响。我们发现重组Eppin调节人类射精中PSA酶的活性，这使我们提出了Eppin-PSA相互作用影响PSA对semenogelin的水解的假设，因此在射精后随着进行性运动的开始而立即具有生理相关性。这一目的将检验抗Eppin抗体破坏Eppin对PSA活性的调节的假设。

DESCRIPTION (provided by applicant): The long-term goals of this research project are to understand the function of Eppin: its interaction with binding partners in a molecular complex on the sperm surface, its relationship with prostate specific antigen (PSA), and its role during the resumption of sperm motility following ejaculation. Very few molecular details are known about the protein-protein interactions that occur on the sperm surface immediately after ejaculation in humans when the resumption of full motility is critical for fertility. As a novel approach to understanding male gamete biology at this critical step, the revised research proposal will seek to understand the interaction of Eppin with its binding partners and its receptor(s) on the human sperm surface, particularly with regard to the resumption of sperm motility following ejaculation. Specific aim #1 will characterize the Eppin protein complex found on the surface of human spermatozoa. Eppin and semenogelin are associated with two other surface proteins, namely clusterin and lactoferrin. Therefore in the discovery phase of this project, specific aim #1 will describe this complex in detail and test our hypothesis that anti-Eppin antibodies will disrupt the Eppin protein complex. Specific aim #2 will identify and characterize the receptor(s) on spermatozoa for Eppin and the Eppin protein complex described in aim #1. Our hypothesis is that Eppin and its complex has a sperm receptor or receptors and their identity will lead to a better understanding of Eppin's function within the complex. Specific aim #3 will characterize the human prostate specific antigen (PSA)-Eppin interaction and its influence on sperm motility. Our discovery that recombinant Eppin modulates PSA enzyme activity in the human ejaculate leads us to propose the hypothesis that Eppin-PSA interaction affects the hydrolysis of semenogelin by PSA and is therefore of physiological relevance immediately after ejaculation as progressive motility begins. This aim will test the hypothesis that anti-Eppin antibodies disrupt Eppin's modulation of PSA activity.