cAMP作为细胞内关键的信号分子，在多种组织中调节着细胞的生长、分化和运动；精子细胞必须经过一个成熟的过程，在信号刺激下其形态，生化和生理发生一系列变化才能发育为功能性精子。然而在模式动物线虫中，cAMP信号与精子成熟和运动之间的调控关系目前还未见报道。本项目从碳酸氢根在线虫精子成熟过程中发挥的重要功能着手，分离鉴定响应碳酸氢根信号的可溶性腺苷酸环化酶(sAC)，研究sAC活性调节及其合成的cAMP信号分子传递网络在精子成熟过程中的调控作用；分析胞内cAMP水平在精子成熟过程中的动态变化。同时研究磷酸二酯酶(PDEs)对胞内cAMP水平的调控及其对精子成熟的影响，探讨钙信号与cAMP信号之间的调控关系，全面解析cAMP信号通路对线虫精子成熟和运动的调节机理。预期研究结果不仅对于控制动植物寄生虫的传播，治疗不育等具有重要的理论指导意义，更是填补了cAMP及腺苷酸环化酶在线虫研究中的空白。

The second messenger cyclic adenosine 3’,5’ monophosphate (cAMP), modulates cell proliferation, differentiation and migration in various tissues of organisms ranging from bacteria to higher eukaryotes. The sperm must undergo a maturation process called sperm activation in nematode or capacitation in mammalian, which consists of morphological, biochemical and physiological processes in sperm in order to acquire their fertilizing potential. It has been demonstrated that bicarbonate stimulates an evolutionarily conserved soluble adenylyl cyclase (sAC) from bacteria to mammals to produce the cAMP. sAC was first identified in rat sperm and is essentially required for the sperm maturation in mammals. The bicarbonate is also essential for sperm maturation in nematode Ascaris suum, however, the roles bicarbonate plays during sperm maturation remain elusive. The previous bioinformatic studies indicate that no sAC homologs exist in fly and worm. We propose to continue our investigation of the mechanism(s) of sperm maturation in nematode Ascaris suum, with an emphasis on the signal transduction initiated by the extracellular bicarbonate. These studies will involve a range of experimental techniques and will require an integration of project objectives from the molecular to cellular levels. We plan to focus our attention on the following aims: (a) examine the roles of bicarbonate on nematode sperm activation and investigate whether a bicarbonate-responsive sAC-like sensor functions during sperm activation; (b) analyze the intracellular cAMP level changes induced by bicarbonate in nematode sperm and study the sAC-cAMP signal pathway functions during sperm maturation; (c) investigate the role of the cAMP-specific phosphodiesterases (PDEs) during sperm maturation; (d) the crosstalk between the cAMP and calcium is also the focus of this proposal. These studies will provide the framework for future studies on the evolution and function of bicarbonate-sensing sACs ranging from bacteria to higher animals. Information from this nature will likely potentiate a wide range of fundamental biological studies and might provide clues for developing new strategies for parasite control and nontoxic male contraceptive.