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：其与精子表面分子复合物中的结合伴侣的相互作用，其与前列腺特异性抗原（PSA）的关系，以及其在射精后精子活力恢复过程中的作用。人类射精后精子表面发生的蛋白质-蛋白质相互作用的分子细节知之甚少，而恢复完全的运动能力对生育力至关重要。作为一种新的方法来了解男性配子生物学在这一关键步骤，修订后的研究计划将寻求了解Eppin与其结合伙伴及其受体（S）在人类精子表面的相互作用，特别是关于精子活力的恢复射精后。具体目标#1将表征在人类精子表面发现的Eppin蛋白复合物。Eppin和semenogelin与另外两种表面蛋白，即clusterin和lactoferrin相关。因此，在本项目的发现阶段，具体目标#1将详细描述这种复合物，并测试我们的假设，即抗Eppin抗体将破坏Eppin蛋白复合物。具体目标#2将鉴定和表征目标#1中描述的Eppin和Eppin蛋白复合物在精子上的受体。我们的假设是，Eppin及其复合物具有精子受体或受体，它们的身份将导致更好地了解Eppin在复合物中的功能。具体目标#3将表征人前列腺特异性抗原（PSA）-Eppin相互作用及其对精子活力的影响。我们的发现，重组Eppin调节PSA酶的活性在人类射精导致我们提出的假设，Eppin-PSA相互作用影响PSA的精液凝固蛋白的水解，因此是生理相关的射精后立即开始进行性运动。这一目标将测试的假设，即抗Eppin抗体破坏Eppin的PSA活性的调制。

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.