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, 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....

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Detalhes bibliográficos
Autores: Luque, Guillermina Maria, Xu, Xinran, Romarowski, Ana, Gervasi, María G., Orta, Gerardo, De la Vega Beltrán, José L., Stival, Cintia Estefanía, Gilio, Nicolás, D'alotto Moreno, Tomas, Krapf, Dario, Visconti, Pablo E., Krapf, Diego, Darszon, Alberto, Buffone, Mariano Gabriel
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/140789
Acesso em linha:http://hdl.handle.net/11336/140789
Access Level:acceso abierto
Palavra-chave:CALCIUM
CAPACITATION
HYPERACTIVATION
SPERM
SUPER-RESOLUTION
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descrição
Resumo: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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