[Soluble forms of adenylyl cyclases of spermatozoa]

Soluble (cytosolic) forms of adenylyl cyclases (sAC), the enzymes catalyzing the conversion of ATP to the second messenger cAMP, play a key role in the regulation of spermatogenesis, control maturation of spermatozoa in the epididymis and their capacitation in the female genital tract, which determines their ability to fertilize. In the last years the significant progress was made in the study of the structural and functional organization and regulatory properties of sAC, their localization in the spermatozoa as well as in the investigation of intracellular cascades functionally coupled with sAC, including protein kinase A, cAMP-dependent phosphodiesterase, non-receptor tyrosine kinases, tyrosine phosphatases, transcription factors of CREB/CREM-family. The molecular mechanisms involved in the regulation of the intracellular concentration of bicarbonate anions, the main endogenous activators of sAC, were deciphered. Many evidences were obtained that the decrease of functional activity of sAC and signaling cascades and effector proteins coupled to it, as well as bicarbonate anion transporters lead to disturbances of spermatogenesis. As a consequence, the development of approaches for controlling the activity of sAC in spermatozoa is one of the priority ways to treat dysfunctions of the male reproductive system. Present review is devoted to advances in the study of soluble forms of AC and functionally coupled to them signaling cascades and effector proteins in the spermatozoa, as well as to the unresolved issues in this area.