SOLUBLE ADENYLYL CYCLASE ACTIVITY IN MALE GERM CELLS

描述：（改编自申请人的摘要）cAMP，一种几乎通用的 信号分子，由腺苷酸家族从ATP合成 环化酶（AC）。在哺乳动物中，有两种类型的AC。一种形式跨越了 它是由一个基因家族编码的，该基因家族由九个相关的 跨膜AC（tmAC）。这些都是由G蛋白和其他第二 使者私家侦探最近发现了第二种哺乳动物AC， 可溶性AC（sAC）对已知的tmAC调节剂不敏感， 不具有跨膜结构域。tmAC和sAC似乎介导相反的 对细胞增殖的影响，并通过 药理学试剂。sAC活性由碳酸氢根离子直接调节。 由于sAC优先在雄性生殖细胞中表达，并且是唯一已知的 研究人员提出， 它是一个很好的候选人，在精子活力方面发挥作用， 和顶体反应。拟议的研究将确定 sAC调节和酶学特征以及使用药理学和 遗传学方法来测试sAC在生殖功能中的作用。长期 计划包括开发sAC作为药理学的潜在目标， 影响生育力的疗法。

DESCRIPTION: (Adapted from the applicant's abstract) cAMP, a nearly universal signaling molecule, is synthesized from ATP by a broad family of adenylyl cyclases (AC). In mammals, there are two types of AC. One form spans the membrane and is encoded by a gene family consisting of nine related transmembrane ACs (tmAC). These are regulated by G proteins and other second messengers. The P.I. has recently identified a second type of mammalian AC, soluble AC (sAC) that is insensitive to the known modulators of tmACs and does not possess membrane spanning domains. tmAC and sAC appear to mediate opposite effects on cellular proliferation and are differentially modulated by pharmacological agents. sAC activity is directly regulated by bicarbonate ions. Since sAC is preferentially expressed in male germ cells and is the only known bicarbonate stimulated adenylyl cyclase in mammals, the investigators propose that it is an excellent candidate to play roles in aspects of sperm motility, capacitiation and the acrosome reaction. The proposed studies will determine the regulatory and enzymological profile of sAC and use pharmacological and genetic approaches to test the role of sAC in reproductive function. Long term plans include developing sAC as a potential target for pharmacological therapeutics affecting fertility.