Structure & Function of Epididymis and Vas Deferens

描述（申请人提供）：请求资金研究Crisp-1蛋白的具体功能。Crisp-1在附睾中产生，并在通过该器官的过程中与精子结合。与已知的ryanodine受体激动剂的高度相似性表明Crisp-1可能在离子通道调节中起作用。钙浓度的变化是精子获得能力和进行顶体反应准备受精所必需的。大鼠精子的体外获能研究表明，当Crisp-1存在时，精子被禁止获能。具体目标集中于确定Crisp-1抑制获能的机制，鉴定精子上Crisp-1的受体，鉴定Crisp-1活性位点，以及研究Crisp家族其他成员模仿Crisp-1作用的能力。 Crisp-1还将测试其抑制人类精子获能和顶体反应的能力。最后，将检查Crisp-1对卵的潜在作用，例如调节皮质颗粒融合的能力。这些研究将为我们理解精子功能做出重大贡献，也可能对男性不育和避孕开发具有潜在的应用价值。

DESCRIPTION (provided by applicant): Funds are requested to study the specific functions of the Crisp-1 protein. Crisp-1 is produced in the epididymis and associates with the sperm during transit through the organ. The high similarity to a known ryanodine receptor agonist suggests that Crisp-1 may have a role in ion channel regulation. Changes in calcium concentrations are required for sperm to become capacitated and undergo the acrosome reaction in preparation for fertilization. In vitro capacitation studies of rat sperm show that when Crisp-1 is present, sperm are prohibited from capacitating. The specific aims focus on determining the mechanisms involved in the inhibition of capacitation by Crisp-l, identification of the receptor for Crisp-1 on sperm, identification of the Crisp-1 active site, and investigation of the ability of other members of the Crisp family to mimic the actions of Crisp-1. Crisp-1 will also be tested for its ability to inhibit capacitation and the acrosome reaction in human sperm. Finally, potential actions of Crisp-1 on the egg, such as the ability to regulate cortical granule fusion, will be examined. The proposed studies will provide significant contributions to our understanding of sperm function and may also have potential application to male infertility and contraceptive development.