Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation

Autores
Puga Molina, Lis del Carmen; Pinto, Nicolás Alejandro; Torres Rodríguez, Paulina; Romarowski, Ana; Vicens Sanchez, Alberto; Visconti, Pablo E.; Darszon, Alberto; Treviño, Claudia L.; Buffone, Mariano Gabriel
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mammalian sperm require to spend a limited period of time in the female reproductive tract to become competent to fertilize in a process called capacitation. It is well established that HCO3 − is essential for capacitation because it activates the atypical soluble adenylate cyclase ADCY10 leading to cAMP production, and promotes alkalinization of cytoplasm, and membrane hyperpolarization. However, how HCO3 − is transported into the sperm is not well understood. There is evidence that CFTR activity is involved in the human sperm capacitation but how this channel is integrated in the complex signaling cascades associated with this process remains largely unknown. In the present work, we have analyzed the extent to which CFTR regulates different events in human sperm capacitation. We observed that inhibition of CFTR affects HCO3 −-entrance dependent events resulting in lower PKA activity. CFTR inhibition also affected cAMP/PKA-downstream events such as the increase in tyrosine phosphorylation, hyperactivated motility, and acrosome reaction. In addition, we demonstrated for the first time, that CFTR and PKA activity are essential for the regulation of intracellular pH, and membrane potential in human sperm. Addition of permeable cAMP partially recovered all the PKA-dependent events altered in the presence of inh-172 which is consistent with a role of CFTR upstream of PKA activation.
Fil: Puga Molina, Lis del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Pinto, Nicolás Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Torres Rodríguez, Paulina. Universidad Nacional Autónoma de México; México
Fil: Romarowski, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vicens Sanchez, Alberto. Universidad Nacional Autónoma de México; México
Fil: Visconti, Pablo E.. University of Massachussets; Estados Unidos
Fil: Darszon, Alberto. Universidad Nacional Autónoma de México; México
Fil: Treviño, Claudia L.. Universidad Nacional Autónoma de México; México
Fil: Buffone, Mariano Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
Cftr
Humans
Alkalinization
Sperm Capacitation
Cyclic Amp
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/41270
Acceder
id CONICETDig_b494906451b4cfdf8b9e896d5a83a049
oai_identifier_str oai:ri.conicet.gov.ar:11336/41270
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitationPuga Molina, Lis del CarmenPinto, Nicolás AlejandroTorres Rodríguez, PaulinaRomarowski, AnaVicens Sanchez, AlbertoVisconti, Pablo E.Darszon, AlbertoTreviño, Claudia L.Buffone, Mariano GabrielCftrHumansAlkalinizationSperm CapacitationCyclic Amphttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Mammalian sperm require to spend a limited period of time in the female reproductive tract to become competent to fertilize in a process called capacitation. It is well established that HCO3 − is essential for capacitation because it activates the atypical soluble adenylate cyclase ADCY10 leading to cAMP production, and promotes alkalinization of cytoplasm, and membrane hyperpolarization. However, how HCO3 − is transported into the sperm is not well understood. There is evidence that CFTR activity is involved in the human sperm capacitation but how this channel is integrated in the complex signaling cascades associated with this process remains largely unknown. In the present work, we have analyzed the extent to which CFTR regulates different events in human sperm capacitation. We observed that inhibition of CFTR affects HCO3 −-entrance dependent events resulting in lower PKA activity. CFTR inhibition also affected cAMP/PKA-downstream events such as the increase in tyrosine phosphorylation, hyperactivated motility, and acrosome reaction. In addition, we demonstrated for the first time, that CFTR and PKA activity are essential for the regulation of intracellular pH, and membrane potential in human sperm. Addition of permeable cAMP partially recovered all the PKA-dependent events altered in the presence of inh-172 which is consistent with a role of CFTR upstream of PKA activation.Fil: Puga Molina, Lis del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pinto, Nicolás Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Torres Rodríguez, Paulina. Universidad Nacional Autónoma de México; MéxicoFil: Romarowski, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vicens Sanchez, Alberto. Universidad Nacional Autónoma de México; MéxicoFil: Visconti, Pablo E.. University of Massachussets; Estados UnidosFil: Darszon, Alberto. Universidad Nacional Autónoma de México; MéxicoFil: Treviño, Claudia L.. Universidad Nacional Autónoma de México; MéxicoFil: Buffone, Mariano Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaWiley Periodicals Inc.2017-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/41270Puga Molina, Lis del Carmen; Pinto, Nicolás Alejandro; Torres Rodríguez, Paulina; Romarowski, Ana; Vicens Sanchez, Alberto; et al.; Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation; Wiley Periodicals Inc.; Journal of Cellular Physiology; 232; 6; 6-2017; 1404-14140021-95411097-4652CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.25634info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.25634info:eu-repo/semantics/altIdentifier/pmid/27714810info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:03:19Zoai:ri.conicet.gov.ar:11336/41270instacron: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:34982025-09-10 13:03:19.882CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation
title Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation
spellingShingle Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation
Puga Molina, Lis del Carmen
Cftr
Humans
Alkalinization
Sperm Capacitation
Cyclic Amp
title_short Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation
title_full Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation
title_fullStr Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation
title_full_unstemmed Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation
title_sort Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation
dc.creator.none.fl_str_mv Puga Molina, Lis del Carmen
Pinto, Nicolás Alejandro
Torres Rodríguez, Paulina
Romarowski, Ana
Vicens Sanchez, Alberto
Visconti, Pablo E.
Darszon, Alberto
Treviño, Claudia L.
Buffone, Mariano Gabriel
author Puga Molina, Lis del Carmen
author_facet Puga Molina, Lis del Carmen
Pinto, Nicolás Alejandro
Torres Rodríguez, Paulina
Romarowski, Ana
Vicens Sanchez, Alberto
Visconti, Pablo E.
Darszon, Alberto
Treviño, Claudia L.
Buffone, Mariano Gabriel
author_role author
author2 Pinto, Nicolás Alejandro
Torres Rodríguez, Paulina
Romarowski, Ana
Vicens Sanchez, Alberto
Visconti, Pablo E.
Darszon, Alberto
Treviño, Claudia L.
Buffone, Mariano Gabriel
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cftr
Humans
Alkalinization
Sperm Capacitation
Cyclic Amp
topic Cftr
Humans
Alkalinization
Sperm Capacitation
Cyclic Amp
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Mammalian sperm require to spend a limited period of time in the female reproductive tract to become competent to fertilize in a process called capacitation. It is well established that HCO3 − is essential for capacitation because it activates the atypical soluble adenylate cyclase ADCY10 leading to cAMP production, and promotes alkalinization of cytoplasm, and membrane hyperpolarization. However, how HCO3 − is transported into the sperm is not well understood. There is evidence that CFTR activity is involved in the human sperm capacitation but how this channel is integrated in the complex signaling cascades associated with this process remains largely unknown. In the present work, we have analyzed the extent to which CFTR regulates different events in human sperm capacitation. We observed that inhibition of CFTR affects HCO3 −-entrance dependent events resulting in lower PKA activity. CFTR inhibition also affected cAMP/PKA-downstream events such as the increase in tyrosine phosphorylation, hyperactivated motility, and acrosome reaction. In addition, we demonstrated for the first time, that CFTR and PKA activity are essential for the regulation of intracellular pH, and membrane potential in human sperm. Addition of permeable cAMP partially recovered all the PKA-dependent events altered in the presence of inh-172 which is consistent with a role of CFTR upstream of PKA activation.
Fil: Puga Molina, Lis del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Pinto, Nicolás Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Torres Rodríguez, Paulina. Universidad Nacional Autónoma de México; México
Fil: Romarowski, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Vicens Sanchez, Alberto. Universidad Nacional Autónoma de México; México
Fil: Visconti, Pablo E.. University of Massachussets; Estados Unidos
Fil: Darszon, Alberto. Universidad Nacional Autónoma de México; México
Fil: Treviño, Claudia L.. Universidad Nacional Autónoma de México; México
Fil: Buffone, Mariano Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Mammalian sperm require to spend a limited period of time in the female reproductive tract to become competent to fertilize in a process called capacitation. It is well established that HCO3 − is essential for capacitation because it activates the atypical soluble adenylate cyclase ADCY10 leading to cAMP production, and promotes alkalinization of cytoplasm, and membrane hyperpolarization. However, how HCO3 − is transported into the sperm is not well understood. There is evidence that CFTR activity is involved in the human sperm capacitation but how this channel is integrated in the complex signaling cascades associated with this process remains largely unknown. In the present work, we have analyzed the extent to which CFTR regulates different events in human sperm capacitation. We observed that inhibition of CFTR affects HCO3 −-entrance dependent events resulting in lower PKA activity. CFTR inhibition also affected cAMP/PKA-downstream events such as the increase in tyrosine phosphorylation, hyperactivated motility, and acrosome reaction. In addition, we demonstrated for the first time, that CFTR and PKA activity are essential for the regulation of intracellular pH, and membrane potential in human sperm. Addition of permeable cAMP partially recovered all the PKA-dependent events altered in the presence of inh-172 which is consistent with a role of CFTR upstream of PKA activation.
publishDate 2017
dc.date.none.fl_str_mv 2017-06
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/11336/41270
Puga Molina, Lis del Carmen; Pinto, Nicolás Alejandro; Torres Rodríguez, Paulina; Romarowski, Ana; Vicens Sanchez, Alberto; et al.; Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation; Wiley Periodicals Inc.; Journal of Cellular Physiology; 232; 6; 6-2017; 1404-1414
0021-9541
1097-4652
CONICET Digital
CONICET
url http://hdl.handle.net/11336/41270
identifier_str_mv Puga Molina, Lis del Carmen; Pinto, Nicolás Alejandro; Torres Rodríguez, Paulina; Romarowski, Ana; Vicens Sanchez, Alberto; et al.; Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation; Wiley Periodicals Inc.; Journal of Cellular Physiology; 232; 6; 6-2017; 1404-1414
0021-9541
1097-4652
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.25634
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.25634
info:eu-repo/semantics/altIdentifier/pmid/27714810
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Periodicals Inc.
publisher.none.fl_str_mv Wiley Periodicals Inc.
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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score 12.993085

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