Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways

Autores
Navarrete, Felipe A.; García Vázquez, Francisco A.; Alvau, Antonio; Escoffier, Jessica; Krapf, Dario; Sánchez Cárdenas, Claudia; Salicioni, Ana M.; Darszon, Alberto; Visconti, Pablo E.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mammalian sperm acquire fertilizing ability in the female tract in a process known as capacitation. At the molecular level, capacitation is associated with up-regulation of a cAMP-dependent pathway, changes in intracellular pH, intracellular Ca2+, and an increase in tyrosine phosphorylation. How these signaling systems interact during capacitation is not well understood. Results presented in this study indicate that Ca2+ ions have a biphasic role in the regulation of cAMP-dependent signaling. Media without added Ca2+ salts (nominal zero Ca2+) still contain micromolar concentrations of this ion. Sperm incubated in this medium did not undergo PKA activation or the increase in tyrosine phosphorylation suggesting that these phosphorylation pathways require Ca2+. However, chelation of the extracellular Ca2+ traces by EGTA induced both cAMP-dependent phosphorylation and the increase in tyrosine phosphorylation. The EGTA effect in nominal zero Ca2+ media was mimicked by two calmodulin antagonists, W7 and calmidazolium, and by the calcineurin inhibitor cyclosporine A. These results suggest that Ca2+ ions regulate sperm cAMP and tyrosine phosphorylation pathways in a biphasic manner and that some of its effects are mediated by calmodulin. Interestingly, contrary to wild-type mouse sperm, sperm from CatSper1 KO mice underwent PKA activation and an increase in tyrosine phosphorylation upon incubation in nominal zero Ca2+ media. Therefore, sperm lacking Catsper Ca2+ channels behave as wild-type sperm incubated in the presence of EGTA. This latter result suggests that Catsper transports the Ca2+ involved in the regulation of cAMP-dependent and tyrosine phosphorylation pathways required for sperm capacitation.
Fil: Navarrete, Felipe A.. University of Massachusetts; Estados Unidos
Fil: García Vázquez, Francisco A.. University of Massachusetts; Estados Unidos. Universidad de Murcia; España
Fil: Alvau, Antonio. University of Massachusetts; Estados Unidos
Fil: Escoffier, Jessica. University of Massachusetts; Estados Unidos
Fil: Krapf, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Sánchez Cárdenas, Claudia. Universidad Nacional Autónoma de México; México
Fil: Salicioni, Ana M.. University of Massachusetts; Estados Unidos
Fil: Darszon, Alberto. Universidad Nacional Autónoma de México; México
Fil: Visconti, Pablo E.. University of Massachusetts; Estados Unidos
Materia
Sperm Capacitation
Calcium
Pka
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/21651

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network_name_str CONICET Digital (CONICET)
spelling Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling PathwaysNavarrete, Felipe A.García Vázquez, Francisco A.Alvau, AntonioEscoffier, JessicaKrapf, DarioSánchez Cárdenas, ClaudiaSalicioni, Ana M.Darszon, AlbertoVisconti, Pablo E.Sperm CapacitationCalciumPkahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Mammalian sperm acquire fertilizing ability in the female tract in a process known as capacitation. At the molecular level, capacitation is associated with up-regulation of a cAMP-dependent pathway, changes in intracellular pH, intracellular Ca2+, and an increase in tyrosine phosphorylation. How these signaling systems interact during capacitation is not well understood. Results presented in this study indicate that Ca2+ ions have a biphasic role in the regulation of cAMP-dependent signaling. Media without added Ca2+ salts (nominal zero Ca2+) still contain micromolar concentrations of this ion. Sperm incubated in this medium did not undergo PKA activation or the increase in tyrosine phosphorylation suggesting that these phosphorylation pathways require Ca2+. However, chelation of the extracellular Ca2+ traces by EGTA induced both cAMP-dependent phosphorylation and the increase in tyrosine phosphorylation. The EGTA effect in nominal zero Ca2+ media was mimicked by two calmodulin antagonists, W7 and calmidazolium, and by the calcineurin inhibitor cyclosporine A. These results suggest that Ca2+ ions regulate sperm cAMP and tyrosine phosphorylation pathways in a biphasic manner and that some of its effects are mediated by calmodulin. Interestingly, contrary to wild-type mouse sperm, sperm from CatSper1 KO mice underwent PKA activation and an increase in tyrosine phosphorylation upon incubation in nominal zero Ca2+ media. Therefore, sperm lacking Catsper Ca2+ channels behave as wild-type sperm incubated in the presence of EGTA. This latter result suggests that Catsper transports the Ca2+ involved in the regulation of cAMP-dependent and tyrosine phosphorylation pathways required for sperm capacitation.Fil: Navarrete, Felipe A.. University of Massachusetts; Estados UnidosFil: García Vázquez, Francisco A.. University of Massachusetts; Estados Unidos. Universidad de Murcia; EspañaFil: Alvau, Antonio. University of Massachusetts; Estados UnidosFil: Escoffier, Jessica. University of Massachusetts; Estados UnidosFil: Krapf, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Sánchez Cárdenas, Claudia. Universidad Nacional Autónoma de México; MéxicoFil: Salicioni, Ana M.. University of Massachusetts; Estados UnidosFil: Darszon, Alberto. Universidad Nacional Autónoma de México; MéxicoFil: Visconti, Pablo E.. University of Massachusetts; Estados UnidosWiley2015-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/21651Navarrete, Felipe A.; García Vázquez, Francisco A.; Alvau, Antonio; Escoffier, Jessica; Krapf, Dario; et al.; Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways; Wiley; Journal Of Cellular Physiology; 230; 8; 4-2015; 1758-17690021-9541CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.24873info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jcp.24873/abstractinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752735/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:30Zoai:ri.conicet.gov.ar:11336/21651instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:08:30.489CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways
title Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways
spellingShingle Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways
Navarrete, Felipe A.
Sperm Capacitation
Calcium
Pka
title_short Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways
title_full Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways
title_fullStr Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways
title_full_unstemmed Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways
title_sort Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways
dc.creator.none.fl_str_mv Navarrete, Felipe A.
García Vázquez, Francisco A.
Alvau, Antonio
Escoffier, Jessica
Krapf, Dario
Sánchez Cárdenas, Claudia
Salicioni, Ana M.
Darszon, Alberto
Visconti, Pablo E.
author Navarrete, Felipe A.
author_facet Navarrete, Felipe A.
García Vázquez, Francisco A.
Alvau, Antonio
Escoffier, Jessica
Krapf, Dario
Sánchez Cárdenas, Claudia
Salicioni, Ana M.
Darszon, Alberto
Visconti, Pablo E.
author_role author
author2 García Vázquez, Francisco A.
Alvau, Antonio
Escoffier, Jessica
Krapf, Dario
Sánchez Cárdenas, Claudia
Salicioni, Ana M.
Darszon, Alberto
Visconti, Pablo E.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Sperm Capacitation
Calcium
Pka
topic Sperm Capacitation
Calcium
Pka
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Mammalian sperm acquire fertilizing ability in the female tract in a process known as capacitation. At the molecular level, capacitation is associated with up-regulation of a cAMP-dependent pathway, changes in intracellular pH, intracellular Ca2+, and an increase in tyrosine phosphorylation. How these signaling systems interact during capacitation is not well understood. Results presented in this study indicate that Ca2+ ions have a biphasic role in the regulation of cAMP-dependent signaling. Media without added Ca2+ salts (nominal zero Ca2+) still contain micromolar concentrations of this ion. Sperm incubated in this medium did not undergo PKA activation or the increase in tyrosine phosphorylation suggesting that these phosphorylation pathways require Ca2+. However, chelation of the extracellular Ca2+ traces by EGTA induced both cAMP-dependent phosphorylation and the increase in tyrosine phosphorylation. The EGTA effect in nominal zero Ca2+ media was mimicked by two calmodulin antagonists, W7 and calmidazolium, and by the calcineurin inhibitor cyclosporine A. These results suggest that Ca2+ ions regulate sperm cAMP and tyrosine phosphorylation pathways in a biphasic manner and that some of its effects are mediated by calmodulin. Interestingly, contrary to wild-type mouse sperm, sperm from CatSper1 KO mice underwent PKA activation and an increase in tyrosine phosphorylation upon incubation in nominal zero Ca2+ media. Therefore, sperm lacking Catsper Ca2+ channels behave as wild-type sperm incubated in the presence of EGTA. This latter result suggests that Catsper transports the Ca2+ involved in the regulation of cAMP-dependent and tyrosine phosphorylation pathways required for sperm capacitation.
Fil: Navarrete, Felipe A.. University of Massachusetts; Estados Unidos
Fil: García Vázquez, Francisco A.. University of Massachusetts; Estados Unidos. Universidad de Murcia; España
Fil: Alvau, Antonio. University of Massachusetts; Estados Unidos
Fil: Escoffier, Jessica. University of Massachusetts; Estados Unidos
Fil: Krapf, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Sánchez Cárdenas, Claudia. Universidad Nacional Autónoma de México; México
Fil: Salicioni, Ana M.. University of Massachusetts; Estados Unidos
Fil: Darszon, Alberto. Universidad Nacional Autónoma de México; México
Fil: Visconti, Pablo E.. University of Massachusetts; Estados Unidos
description Mammalian sperm acquire fertilizing ability in the female tract in a process known as capacitation. At the molecular level, capacitation is associated with up-regulation of a cAMP-dependent pathway, changes in intracellular pH, intracellular Ca2+, and an increase in tyrosine phosphorylation. How these signaling systems interact during capacitation is not well understood. Results presented in this study indicate that Ca2+ ions have a biphasic role in the regulation of cAMP-dependent signaling. Media without added Ca2+ salts (nominal zero Ca2+) still contain micromolar concentrations of this ion. Sperm incubated in this medium did not undergo PKA activation or the increase in tyrosine phosphorylation suggesting that these phosphorylation pathways require Ca2+. However, chelation of the extracellular Ca2+ traces by EGTA induced both cAMP-dependent phosphorylation and the increase in tyrosine phosphorylation. The EGTA effect in nominal zero Ca2+ media was mimicked by two calmodulin antagonists, W7 and calmidazolium, and by the calcineurin inhibitor cyclosporine A. These results suggest that Ca2+ ions regulate sperm cAMP and tyrosine phosphorylation pathways in a biphasic manner and that some of its effects are mediated by calmodulin. Interestingly, contrary to wild-type mouse sperm, sperm from CatSper1 KO mice underwent PKA activation and an increase in tyrosine phosphorylation upon incubation in nominal zero Ca2+ media. Therefore, sperm lacking Catsper Ca2+ channels behave as wild-type sperm incubated in the presence of EGTA. This latter result suggests that Catsper transports the Ca2+ involved in the regulation of cAMP-dependent and tyrosine phosphorylation pathways required for sperm capacitation.
publishDate 2015
dc.date.none.fl_str_mv 2015-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/21651
Navarrete, Felipe A.; García Vázquez, Francisco A.; Alvau, Antonio; Escoffier, Jessica; Krapf, Dario; et al.; Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways; Wiley; Journal Of Cellular Physiology; 230; 8; 4-2015; 1758-1769
0021-9541
CONICET Digital
CONICET
url http://hdl.handle.net/11336/21651
identifier_str_mv Navarrete, Felipe A.; García Vázquez, Francisco A.; Alvau, Antonio; Escoffier, Jessica; Krapf, Dario; et al.; Biphasic Role of Calcium in Mouse Sperm Capacitation Signaling Pathways; Wiley; Journal Of Cellular Physiology; 230; 8; 4-2015; 1758-1769
0021-9541
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.24873
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jcp.24873/abstract
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752735/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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