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dc.contributor.author
Battistone, Maria Agustina
dc.contributor.author
Da Ros, Vanina Gabriela
dc.contributor.author
Salicioni, A.
dc.contributor.author
Navarrete, F.
dc.contributor.author
Krapf, Dario
dc.contributor.author
Visconti, P. E.
dc.contributor.author
Cuasnicu, Patricia Sara
dc.date.available
2015-09-30T16:37:09Z
dc.date.issued
2013-04-29
dc.identifier.citation
Battistone, Maria Agustina; Da Ros, Vanina Gabriela; Salicioni, A.; Navarrete, F.; Krapf, Dario; et al.; Functional human sperm capacitation requires both bicarbonate dependent-PKA activation and down-regulation of Ser/Thr phosphatases by Src family kinases; Oxford University Press; Molecular Human Reproduction.; 19; 9; 29-4-2013; 570-580
dc.identifier.issn
1360-9947
dc.identifier.uri
http://hdl.handle.net/11336/2218
dc.description.abstract
In all mammalian species studied so far, sperm capacitation correlates with an increase in protein tyrosine (Tyr) phosphorylation mediated by a bicarbonate-dependent cAMP/PKA pathway. Recent studies in mice revealed however that a Src Family Kinase (SFK) induced inactivation of serine/threonine (Ser/Thr) phosphatases is also involved in the signaling pathways leading to Tyr phosphorylation. In view of these observations and with the aim of getting a better understanding of the signaling pathways involved in human sperm capacitation, in the present work we investigated the involvement of both the cAMP/PKA and SFK/phosphatase pathways in relation to the capacitation state of the cells. For this purpose, different signaling events and sperm functional parameters were analyzed as a function of capacitation time. Results revealed a very early bicarbonate-dependent activation of PKA indicated by the rapid (1 min) increase in both phospho-PKA substrates and cAMP levels (p<0.05). However, a complete pattern of Tyr phosphorylation was detected only after 6 h-incubation at which time sperm exhibited the ability to undergo the acrosome reaction (AR) and to penetrate zona-free hamster eggs. Sperm capacitated in the presence of the SFK inhibitor SKI606 showed a decrease in both PKA substrate and Tyr phosphorylation levels which was overcome by exposure of sperm to the Ser/Thr phosphatase inhibitor okadaic acid (OA). However, OA was unable to induce phosphorylation when sperm were incubated under PKA-inhibitory conditions (i.e. in the absence of bicarbonate or presence of PKA inhibitor). Moreover, the increase in PKA activity by exposure to a cAMP analogue and a phosphodiesterase inhibitor did not overcome the inhibition produced by SKI606. Whereas the presence of SKI606 during capacitation produced a negative effect (p<0.05) on sperm motility, progesterone-induced AR and fertilizing ability, none of these inhibitions were observed when sperm were exposed to SKI606 and OA. Interestingly, different concentrations of inhibitors were required to modulate human and mouse capacitation revealing the species-specificity of the molecular mechanisms underlying this process. In conclusion, our results describe for the first time the involvement of both PKA activation and Ser/Thr phosphatase down-regulation in functional human sperm capacitation and provide convincing evidence that early PKA-dependent phosphorylation is the convergent regulatory point between these two signaling pathways.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Oxford University Press
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Capacitation
dc.subject
Human Sperm
dc.subject
Pka
dc.subject
Phosphatase
dc.subject.classification
Bioquímica y Biología Molecular
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Functional human sperm capacitation requires both bicarbonate dependent-PKA activation and down-regulation of Ser/Thr phosphatases by Src family kinases
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2015-09-21T20:20:33Z
dc.identifier.eissn
1460-2407
dc.journal.volume
19
dc.journal.number
9
dc.journal.pagination
570-580
dc.journal.pais
Reino Unido
dc.journal.ciudad
Oxford
dc.conicet.avisoEditorial
This is a pre-copyedited, author-produced PDF of an article accepted for publication in Mol. Hum. Reprod following peer review. The version of recordMol. Hum. Reprod. (2013) 19 (9): 570-580. doi: 10.1093/molehr/gat033 is available online at: http://molehr.oxfordjournals.org/content/19/9/570
dc.description.fil
Fil: Battistone, Maria Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas -conicet. Instituto de Biología y Medicina Experimental (i); Argentina
dc.description.fil
Fil: Da Ros, Vanina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas -conicet. Instituto de Biología y Medicina Experimental (i); Argentina
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Fil: Salicioni, A.. University Of Massachussets; Estados Unidos
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Fil: Navarrete, F.. University Of Massachussets; Estados Unidos
dc.description.fil
Fil: Krapf, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina. Universidad Nacional de Rosario; Argentina
dc.description.fil
Fil: Visconti, P. E.. University Of Massachussets;
dc.description.fil
Fil: Cuasnicu, Patricia Sara. Consejo Nacional de Investigaciones Científicas y Técnicas -conicet. Instituto de Biología y Medicina Experimental (i); Argentina
dc.journal.title
Molecular Human Reproduction.
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://molehr.oxfordjournals.org/content/19/9/570.full
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/10.1093/molehr/gat033
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1093/molehr/gat033
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/pmid/PMC3749807
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749807/


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