CAMP AND CALCIUM DEPENDENT KINASES IN SPERMATOGENESIS

精子发生中的 CAMP 和钙依赖性激酶

• 批准号: 6655306
• 负责人: George STANLEY MCKNIGHT
• 金额: $ 15.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6655306
• 关键词: A kinase anchoring protein; acrosome; calcium; cell transplantation; cyclic AMP; developmental genetics; enzyme inhibitors; enzyme mechanism; enzyme substrate; fertility; gene expression; gene targeting; genetically modified animals; germ cells; histology; laboratory mouse; mass spectrometry; northern blottings; posttranslational modifications; protein kinase A; protein localization; protein structure function; second messengers; sperm motility; spermatogenesis; western blottings

Despite considerable effort and characterization, the precise role of PKA in regulating sperm development and the acquisition of motility and fertilization competence remains unclear. A major roadblock in these studies has been the lack of techniques to manipulate the expression and activity of PKA in sperm cells since no readily accessible cell culture model is available that allows address questions that related to the importance of subcellular localization, PKA activation state, and developmental changes in survival of spermatids (2) Determine the role of C subunit during spermatogenesis (3) Examine the anchoring of RI and its physiological significance during spermatogenesis (4) Identify specific PKA substrates in sperm and develop a mechanism to inhibit sperm PKA in vivo. These studies are relevant to larger questions concerning the treatment of infertility and the development of male-specific contraceptive approaches.

尽管进行了大量的研究和鉴定，但PKA在调节精子发育、获得运动能力和受精能力方面的确切作用仍不清楚。这些研究的一个主要障碍是缺乏操纵PKA在精子细胞中的表达和活性的技术，因为没有现成的细胞培养模型可以解决与亚细胞定位、PKA激活状态、(2)确定C亚基在精子发生过程中的作用(3)研究RI在精子发生过程中的锚定及其生理意义(4)确定精子中特定的PKA底物，并研究体内抑制精子PKA的机制。这些研究与不孕症的治疗和男性专用避孕方法的发展有关。