Cdc42 localized in the CatSper signaling complex regulates cAMP?dependent pathways in mouse sperm

Sperm acquire the ability to fertilize in a process called capacitation and undergo hyperactivation, change motility pattern, which depends on Ca2+ transport by CatSper channels. is essential for fertilization it subjected complex regulation that not fully understood. Here, we report similar CatSper, Cdc42 distribution principal piece confined four linear domains this localization disrupted CatSper1-null sperm. inhibition impaired activity other Ca2+-dependent downstream events resulting severe compromise of sperm fertilizing potential. We also demonstrate function modulating cAMP production soluble adenylate cyclase (sAC), providing new regulatory mechanism stimulation cAMP-dependent pathway. These results reveal broad mechanistic insight into mammalian sperm, matter critical importance male infertility as well contraception.