The sodium–proton exchangers sNHE and NHE1 control plasma membrane hyperpolarization in mouse sperm

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dc.citation.titleJournal of Biological Chemistry
dc.contributor.orcidhttps://orcid.org/0009-0004-7481-2121
dc.contributor.orcidhttps://orcid.org/0000-0002-2745-8236
dc.contributor.orcidhttps://orcid.org/0000-0002-2833-5553
dc.contributor.orcidhttps://orcid.org/0000-0002-7281-0534
dc.contributor.orcidhttps://orcid.org/0000-0001-7607-1954
dc.creatorNovero, Analia G.
dc.creatorTorres Rodríguez, Paulina
dc.creatorDe la Vega Beltrán, José L.
dc.creatorSchiavi Ehrenhaus, Liza J.
dc.creatorLuque, Guillermina M.
dc.creatorCarruba, Micaela
dc.creatorStival, Cintia Estefanía
dc.creatorGentile, Iñaki
dc.creatorRitagliati, Carla
dc.creatorSanti, Celia M.
dc.creatorNishigaki, Takuya
dc.creatorKrapf, Diego
dc.creatorBuffone, Mariano Gabriel
dc.creatorDarszon, Alberto
dc.creatorTreviño, Claudia L.
dc.creatorKrapf, Darío
dc.date.accessioned2025-02-27T17:44:57Z
dc.date.available2025-02-27T17:44:57Z
dc.date.issued2024-10-24
dc.description.abstractSperm capacitation is a complex process that takes place in the female reproductive tract and empowers mammalian sperm with the competence to fertilize an egg. It consists of an intricate cascade of events that can be mimicked in vitro through incubation in a medium containing essential components, such as bicarbonate, albumin, Ca2+, and energy substrates, among others. Genetic and pharmacological studies have underscored the unique significance of the K+ channel SLO3 in membrane potential hyperpolarization, as evidenced by the infertility of mice lacking its expression. Notably, two key molecular events, sperm hyperpolarization and intracellular alkalinization, are central to the capacitation process. SLO3 is activated by alkalinization. However, the molecular mechanisms responsible for intracellular alkalization and activation of SLO3 are not completely understood. In this study, we examined the impact of Na+/H+ exchangers (NHEs) on mouse sperm membrane hyperpolarization during capacitation. Pharmacological inhibition of the NHE1 blocked membrane hyperpolarization. A similar effect was observed in sperm deficient of the Ca2+ channel CatSper because of NHE1 not being activated by Ca2+. In addition, the sperm-specific NHE (sNHE) KO did not show membrane hyperpolarization upon capacitation or induction with cAMP analogs. Our results show that sNHE is dually modulated by cAMP and membrane hyperpolarization probably through its cyclic nucleotide–binding domain and the voltage-sensor motif, respectively. Together, sNHE and NHE1 provide the alkalinization need for SLO3 activation during capacitation.
dc.description.filFil: Novero, Analia G. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Laboratorio de Medina Reproductiva. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Torres Rodríguez, Paulina. Universidad Nacional Autónoma de México. Instituto de Biotecnología, México.
dc.description.filFil: De la Vega Beltrán, José L. Universidad Nacional Autónoma de México. Instituto de Biotecnología, México.
dc.description.filFil: Schiavi Ehrenhaus, Liza J. Instituto de Biología y Medicina Experimental (IBYME-CONICET); Argentina.
dc.description.filFil: Luque, Guillermina M. Instituto de Biología y Medicina Experimental (IBYME-CONICET); Argentina.
dc.description.filFil: Carruba, Micaela. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Laboratorio de Medina Reproductiva. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Stival, Cintia Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Laboratorio de Medina Reproductiva. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Gentile, Iñaki. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Laboratorio de Medina Reproductiva. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Ritagliati, Carla. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Laboratorio de Medina Reproductiva. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Santi, Celia M. Washington University School of Medicine. Department of Obstetrics and Gynecology; The United States.
dc.description.filFil: Nishigaki, Takuya. Universidad Nacional Autónoma de México. Instituto de Biotecnología, México.
dc.description.filFil: Krapf, Diego. Colorado State University. Department of Electrical and Computer Engineering; The United States.
dc.description.filFil: Buffone, Mariano Gabriel. Instituto de Biología y Medicina Experimental (IBYME-CONICET); Argentina.
dc.description.filFil: Darszon, Alberto. Universidad Nacional Autónoma de México. Instituto de Biotecnología, México.
dc.description.filFil: Treviño, Claudia L. Universidad Nacional Autónoma de México. Instituto de Biotecnología, México.
dc.description.filFil: Krapf, Darío. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Laboratorio de Medina Reproductiva. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.sponsorshipAgencia Nacional de Promoción Científica y Tecnológica: 2017-3217, 2019-1779, 2021-A-0102
dc.description.sponsorshipUniversidad Nacional Autónoma de México. Dirección General de Asuntos del Personal Académico: PAPIIT IN207122, PAPIIT IN200919
dc.description.sponsorshipConsejo Nacional de Ciencia y Tecnología: CF-2023-I-291
dc.description.sponsorshipNational Institutes of Health: RO1HD038082-17A1, R01HD069631, R01HD106968
dc.description.versionpeerreviewed
dc.format.extent1-12
dc.identifier.issn0021-9258
dc.identifier.urihttps://hdl.handle.net/2133/28972
dc.language.isoen
dc.publisherElsevier
dc.relation.publisherversionhttps://doi.org/10.1016/j.jbc.2024.107932
dc.relation.publisherversionhttps://www.jbc.org/article/S0021-9258(24)02434-7/fulltext
dc.rightsopenAccess
dc.rights.holderNovero, Analia G.
dc.rights.holderTorres Rodríguez, Paulina
dc.rights.holderDe la Vega Beltrán, José L.
dc.rights.holderSchiavi Ehrenhaus, Liza J.
dc.rights.holderLuque, Guillermina M.
dc.rights.holderCarruba, Micaela
dc.rights.holderStival, Cintia Estefanía
dc.rights.holderGentile, Iñaki
dc.rights.holderRitagliati, Carla
dc.rights.holderSanti, Celia M.
dc.rights.holderNishigaki, Takuya
dc.rights.holderKrapf, Diego
dc.rights.holderBuffone, Mariano Gabriel
dc.rights.holderDarszon, Alberto
dc.rights.holderTreviño, Claudia L
dc.rights.holderKrapf, Darío
dc.rights.textAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectSodium–proton exchange
dc.subjectSperm
dc.subjectPotassium channel
dc.subjectAdenylate cyclase
dc.subjectCyclic AMP
dc.subjectFertilization
dc.subjectMembrane hyperpolarization
dc.titleThe sodium–proton exchangers sNHE and NHE1 control plasma membrane hyperpolarization in mouse sperm
dc.typearticulo
dc.type.collectionarticulo
dc.type.versionpublishedVersion

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