Your browser doesn't support javascript.
loading
C2CD6 regulates targeting and organization of the CatSper calcium channel complex in sperm flagella.
Yang, Fang; Gracia Gervasi, Maria; Orta, Gerardo; Tourzani, Darya A; De la Vega-Beltrán, Jose Luis; Ruthel, Gordon; Darszon, Alberto; Visconti, Pablo E; Wang, P Jeremy.
Afiliación
  • Yang F; Department of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA.
  • Gracia Gervasi M; Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
  • Orta G; Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, México.
  • Tourzani DA; Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
  • De la Vega-Beltrán JL; Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, México.
  • Ruthel G; Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA.
  • Darszon A; Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, México.
  • Visconti PE; Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
  • Wang PJ; Department of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA.
Development ; 149(2)2022 01 15.
Article en En | MEDLINE | ID: mdl-34919125
The CatSper cation channel is essential for sperm capacitation and male fertility. The multi-subunit CatSper complexes form highly organized calcium signaling nanodomains on flagellar membranes. Here, we report identification of an uncharacterized protein, C2CD6, as a subunit of the mouse CatSper complex. C2CD6 contains a calcium-dependent, membrane-targeting C2 domain. C2CD6 associates with the CatSper calcium-selective, core-forming subunits. Deficiency of C2CD6 depletes the CatSper nanodomains from the flagellum and results in male sterility. C2CD6-deficient sperm are defective in hyperactivation and fail to fertilize oocytes both in vitro and in vivo. CatSper currents are present but at a significantly lower level in C2CD6-deficient sperm. Transient treatments with either Ca2+ ionophore, starvation, or a combination of both restore the fertilization capacity of C2CD6-deficient sperm. C2CD6 interacts with EFCAB9, a pH-dependent calcium sensor in the CatSper complex. We postulate that C2CD6 facilitates incorporation of the CatSper complex into the flagellar plasma membrane and may function as a calcium sensor. The identification of C2CD6 may enable the long-sought reconstitution of the CatSper ion channel complex in a heterologous system for male contraceptive development.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cola del Espermatozoide / Canales de Calcio / Infertilidad Masculina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Development Asunto de la revista: BIOLOGIA / EMBRIOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cola del Espermatozoide / Canales de Calcio / Infertilidad Masculina Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Development Asunto de la revista: BIOLOGIA / EMBRIOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido