Cdc42 localized in the CatSper signaling complex regulates cAMP‐dependent pathways in mouse sperm. Issue 8 (5th July 2021)

• Record Type: Journal Article
• Authors: Luque, Guillermina M.; Xu, Xinran; Romarowski, Ana; Gervasi, María G.; Orta, Gerardo; De la Vega‐Beltrán, José L.; Stival, Cintia; Gilio, Nicolás; Dalotto‐Moreno, Tomás; Krapf, Dario; Visconti, Pablo E.; Krapf, Diego; Darszon, Alberto; Buffone, Mariano G.
• Is Part Of: FASEB journal. Volume 35:Issue 8(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-05
• Subjects: calcium -- capacitation -- hyperactivation -- sperm -- super‐resolution; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202002773RR
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Sperm acquire the ability to fertilize in a process called capacitation and undergo hyperactivation, a change in the motility pattern, which depends on Ca 2+ transport by CatSper channels. CatSper is essential for fertilization and it is subjected to a complex regulation that is not fully understood. Here, we report that similar to CatSper, Cdc42 distribution in the principal piece is confined to four linear domains and this localization is disrupted in CatSper1‐null sperm. Cdc42 inhibition impaired CatSper activity and other Ca 2+ ‐dependent downstream events resulting in a severe compromise of the sperm fertilizing potential. We also demonstrate that Cdc42 is essential for CatSper function by modulating cAMP production by soluble adenylate cyclase (sAC), providing a new regulatory mechanism for the stimulation of CatSper by the cAMP‐dependent pathway. These results reveal a broad mechanistic insight into the regulation of Ca 2+ in mammalian sperm, a matter of critical importance in male infertility as well as in contraception.