Mammalian sperm are not able to fertilize eggs immediately after ejaculation. They acquire fertilization capacity after residing in the female tract for a finite period of time in a process known as capacitation [24, 25]. Initially, capacitation was defined using fertilization as end-point. However, a variety of evidences suggest that the functional changes occurring in the sperm during capacitation are not one event, but a combination of sequential and concomitant processes. Some of these processes occur as soon as the sperm are released from the epididymis, others are slower and are activated only after sperm incubation for a certain period of time in conditions that support the sperm ability to fertilize the egg. These slow events are associated with changes in the motility pattern (e.g. hyperactivation) and with the acquisition of the sperm capacity to undergo an agonist-stimulated acrosome reaction (AR). Although both, fast and slow events are regulated by HCO3- and by a cAMP-dependent pathway, slower events are limited by the release of cholesterol from the sperm plasma membrane. Using the mouse as an experimental model, we have demonstrated that these last events are associated with a protein kinase A (PKA)-dependent increase in the tyrosine (tyr) phosphorylation of a subset of proteins [23, 26]. Simultaneously with our findings, Zeng et al. (1995) reported that capacitation is accompanied by hyperpolarization of the sperm plasma membrane ootential (Em). It has been hypothesized that hyperpolarization is necessary to drive Low Voltage Activated (LVA) Ca2+ T-channels (Cav3) from an inactive state to a closed state that can be activated by agonists such as the zona pellucida (ZP), triggering the AR. Despite these advances, little is known on how these molecular changes are combined to promote capacitation. As part of the first cycle of this grant, we have shown that HCO3-, Na+ and K+ are involved in the regulation of the sperm Em [21, 27, 28] and that Epithelial Na+ channels (ENaC) are present in sperm and play an important role in the regulation of the sperm resting Em [21]. The objective of this proposal is to understand how changes in cAMP, protein phosphorylation and hyperpolarization integrate to promote capacitation. Investigation of the crosstalk between cAMP and the changes in ion permeability is essential to understand the molecular basis of capacitation and to provide novel targets for pharmacological control of the fertilization process.
| Gervasi, María G; Xu, Xinran; Carbajal-Gonzalez, Blanca et al. (2018) The actin cytoskeleton of the mouse sperm flagellum is organized in a helical structure. J Cell Sci 131: |
| Tourzani, Darya A; Paudel, Bidur; Miranda, Patricia V et al. (2018) Changes in Protein O-GlcNAcylation During Mouse Epididymal Sperm Maturation. Front Cell Dev Biol 6:60 |
| Stival, Cintia; Ritagliati, Carla; Xu, Xinran et al. (2018) Disruption of protein kinase A localization induces acrosomal exocytosis in capacitated mouse sperm. J Biol Chem 293:9435-9447 |
| Romarowski, Ana; Velasco Félix, Ángel G; Torres Rodríguez, Paulina et al. (2018) Super-resolution imaging of live sperm reveals dynamic changes of the actin cytoskeleton during acrosomal exocytosis. J Cell Sci 131: |
| Orta, Gerardo; de la Vega-Beltran, José Luis; Martín-Hidalgo, David et al. (2018) CatSper channels are regulated by protein kinase A. J Biol Chem 293:16830-16841 |
| Luque, Guillermina M; Dalotto-Moreno, Tomas; Martín-Hidalgo, David et al. (2018) Only a subpopulation of mouse sperm displays a rapid increase in intracellular calcium during capacitation. J Cell Physiol 233:9685-9700 |
| Puga Molina, Lis C; Pinto, Nicolás A; Torres Rodríguez, Paulina et al. (2017) Essential Role of CFTR in PKA-Dependent Phosphorylation, Alkalinization, and Hyperpolarization During Human Sperm Capacitation. J Cell Physiol 232:1404-1414 |
| Gervasi, M G; Visconti, P E (2017) Molecular changes and signaling events occurring in spermatozoa during epididymal maturation. Andrology 5:204-218 |
| Beltrán, Carmen; Treviño, Claudia L; Mata-Martínez, Esperanza et al. (2016) Role of Ion Channels in the Sperm Acrosome Reaction. Adv Anat Embryol Cell Biol 220:35-69 |
| Stival, Cintia; Puga Molina, Lis del C; Paudel, Bidur et al. (2016) Sperm Capacitation and Acrosome Reaction in Mammalian Sperm. Adv Anat Embryol Cell Biol 220:93-106 |
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