♦ See referenced article, J. Biol. Chem. 2013, 288, 35307–35320
Mammalian sperm cells undergo a process called capacitation, which readies them for fertilization. Cyclic AMP (cAMP) is essential for the process, but its source at the sperm head is unclear. Transmembrane adenylyl cyclases (tmACs) have been speculated to be involved. In this Paper of the Week, a team led by Pablo Visconti at the University of Massachusetts, Amherst, and Alberto Darszon at the Universidad Nacional Autónoma de México demonstrated that tmACs, which are regulated by heterotrimeric stimulatory Gs proteins, exist in the mouse sperm head. Furthermore, the investigators showed that cAMP signaling pathways are compartmentalized in the sperm cell. A pathway with heterotrimeric Gs proteins and tmAC functions in the head; another pathway with the soluble adenylyl cyclase Adcy10 and protein kinase A is responsible for cAMP signaling in the flagellum and controls sperm motility. “This work constitutes the basis toward the understanding of key questions in the regulation of sperm signaling pathways, many of which remain unsolved despite many years of research in the field,” say the authors. “A clear understanding of how capacitation is regulated will benefit future experimental approaches aiming to increase the fertilizing ability of the sperm population, as well as the design of rational contraceptive approaches.” Because both tmACs and Adcy10 are present in somatic cells, the authors add that this study will offer insight into understanding compartmentalization of cAMP pathways in other cell types.
Proposed model for the spatial distribution of cAMP in sperm functions.