Cascadas de señalización involucradas en la capacitación del espermatozoide de mamífero : participación de quinasas y fosfatasas
Mammalian ejaculated sperm become able to fertilize an egg only after they undergo the\ncapacitation process that occurs in the female reproductive tract and leads to an increase\nin protein tyrosine (Tyr) phosphorylation, the occurrence of the acrosome reaction and the\ndevelopment of hyperactivati...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2015
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1411 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1411.dir/1411.PDF |
| Aporte de: |
| Sumario: | Mammalian ejaculated sperm become able to fertilize an egg only after they undergo the\ncapacitation process that occurs in the female reproductive tract and leads to an increase\nin protein tyrosine (Tyr) phosphorylation, the occurrence of the acrosome reaction and the\ndevelopment of hyperactivation. The main aim of this Thesis has been to investigate the\nmolecular mechanisms involved in the different signaling pathways leading to sperm\ncapacitation in mammals. Results revealed the involvement of both PKA activation and\nserine/threonine phosphatase down-regulation by Src family Tyr kinases in functional\nsperm capacitation, and provided convincing evidence that early PKA-dependent\nphosphorylation is the convergent regulatory point between these signaling pathways.\nMoreover, our observations supported that Tyr kinase PYK2, regulated by calcium, is the\nresponsible of integrating different signaling events between PKA-mediated- and Tyr\nphosphorylations and, it is required for achieving functional capacitation. Considering that\ncapacitation involves the release of ?decapacitating factors? among which is CRISP1\n(Cysteine Rich Secretory Protein 1), an epididymal protein identified by our group, we next\nstudied the signaling cascades involved in the regulation of capacitation by CRISP1. Our\nresults, using purified CRISP1 and CRISP1-knockout mice, indicated that this protein\ninhibits the two principal sperm calcium channels, regulating in this way the capacitation\nprocess and hyperactivation. Altogether, our observations contribute to a better\nunderstanding of the mechanisms leading to the acquisition of sperm fertilizing ability as\nwell as to the development of new pharmacological tools for fertility regulation and\ntreatment of human infertility. |
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