Journal
FASEB JOURNAL
Volume 35, Issue 8, Pages -Publisher
WILEY
DOI: 10.1096/fj.202002773RR
Keywords
calcium; capacitation; hyperactivation; sperm; super-resolution
Categories
Funding
- Agencia Nacional de Promocion Cientifica y Tecnologica [PICT 2015-2294, 2015-3164, 2017-3047, 2018-1988]
- Williams Foundation
- Consejo Nacional de Ciencia y Tecnologia (CONACyT - Mexico Fronteras 71)
- Programa de Apoyo a Proyectos de Investigacion e Innovacion Tecnologica UNAM [PAPIIT/DGAPA IN205516]
- UNAM/DGAPA
- IGC
- Rene Baron Foundation
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The study found that Cdc42 and CatSper play crucial roles in sperm, with Cdc42 inhibition affecting CatSper activity and severely compromising the sperm's fertilizing potential. Cdc42 regulates the function of CatSper by modulating the production of cAMP, providing a new regulatory mechanism for stimulating CatSper through the cAMP-dependent pathway.
Sperm acquire the ability to fertilize in a process called capacitation and undergo hyperactivation, a change in the motility pattern, which depends on Ca2+ 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 Ca2+-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 Ca2+ in mammalian sperm, a matter of critical importance in male infertility as well as in contraception.
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