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Regulation of Sperm Capacitation and the Acrosome Reaction by PIP 2 and Actin Modulation.

Breitbart H, Finkelstein M - Asian J. Androl. (2015 Jul-Aug)

Bottom Line: Stimulation of phospholipase C, by Ca 2 + -ionophore or by activating the epidermal-growth-factor-receptor, inhibits tyrosine phosphorylation of gelsolin and enhances enzyme activity.In conclusion, these data indicate that the increase of PIP 2 and/or F-actin in the head during capacitation enhances gelsolin translocation to the head.As a result, the decrease of gelsolin in the tail allows the maintenance of high levels of F-actin in this structure, which is essential for the development of HA motility.

View Article: PubMed Central - PubMed

Affiliation: The Mina and Everard Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.

ABSTRACT
Actin polymerization and development of hyperactivated (HA) motility are two processes that take place during sperm capacitation. Actin polymerization occurs during capacitation and prior to the acrosome reaction, fast F-actin breakdown takes place. The increase in F-actin during capacitation depends upon inactivation of the actin severing protein, gelsolin, by its binding to phosphatydilinositol-4, 5-bisphosphate (PIP 2 ) and its phosphorylation on tyrosine-438 by Src. Activation of gelsolin following its release from PIP 2 is known to cause F-actin breakdown and inhibition of sperm motility, which can be restored by adding PIP 2 to the cells. Reduction of PIP 2 synthesis inhibits actin polymerization and motility, while increasing PIP 2 synthesis enhances these activities. Furthermore, sperm demonstrating low motility contained low levels of PIP 2 and F-actin. During capacitation there was an increase in PIP 2 and F-actin levels in the sperm head and a decrease in the tail. In spermatozoa with high motility, gelsolin was mainly localized to the sperm head before capacitation, whereas in low motility sperm, most of the gelsolin was localized to the tail before capacitation and translocated to the head during capacitation. We also showed that phosphorylation of gelsolin on tyrosine-438 depends upon its binding to PIP 2 . Stimulation of phospholipase C, by Ca 2 + -ionophore or by activating the epidermal-growth-factor-receptor, inhibits tyrosine phosphorylation of gelsolin and enhances enzyme activity. In conclusion, these data indicate that the increase of PIP 2 and/or F-actin in the head during capacitation enhances gelsolin translocation to the head. As a result, the decrease of gelsolin in the tail allows the maintenance of high levels of F-actin in this structure, which is essential for the development of HA motility.

No MeSH data available.


Related in: MedlinePlus

A model describing the biochemical cascade that leads to the acrosome reaction (AR): the binding of capacitated spermatozoa to the egg zona pellucida causes a fast and high increase in intra-spermatozoal Ca2+ concentration. As a result, active PLC catalyses PIP2 hydrolysis to produce IP3 and diacylglycerol (DAG) and the release of bound p-gelsolin. The p-gelsolin undergoes dephosphorylation/activation by tyrosine phosphatase leadin to conversion of F-actin to G-actin. IP3 activates Ca2+ channel in the outer acrosomal membrane which reduces intra-acrosomal Ca2+ leading to the activation of Ca2+- dependent-Ca2+ channel in the plasma membrane which causes further increase in intracellular Ca2+ which together with DAG activate PKC which mediates the acrosome reaction. Also, PKA-dependent PI3K activation occurs towards the end of the capacitation process, involves in the mechanism leding to the AR.
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Figure 5: A model describing the biochemical cascade that leads to the acrosome reaction (AR): the binding of capacitated spermatozoa to the egg zona pellucida causes a fast and high increase in intra-spermatozoal Ca2+ concentration. As a result, active PLC catalyses PIP2 hydrolysis to produce IP3 and diacylglycerol (DAG) and the release of bound p-gelsolin. The p-gelsolin undergoes dephosphorylation/activation by tyrosine phosphatase leadin to conversion of F-actin to G-actin. IP3 activates Ca2+ channel in the outer acrosomal membrane which reduces intra-acrosomal Ca2+ leading to the activation of Ca2+- dependent-Ca2+ channel in the plasma membrane which causes further increase in intracellular Ca2+ which together with DAG activate PKC which mediates the acrosome reaction. Also, PKA-dependent PI3K activation occurs towards the end of the capacitation process, involves in the mechanism leding to the AR.

Mentions: In conclusion, our data suggest the following model (Figures 4 and 5): the relatively small increase in [Ca2+]i during capacitation leads to conformational changes in gelsolin revealing the F-actin binding site. This change and the increase in F-actin and PIP2 in the sperm head, result in gelsolin being translocated to this region of the cell. Nevertheless, the elevation of PIP2 levels and PKA/Src activation, maintain gelsolin in a phosphorylated/inactivated state and actin polymerization occurs. The increase in F-actin in the tail leads to the development of hyper-activated motility as part of the capacitation process. Immediately prior to the AR (Figure 5), the egg zona-pellucida activates GPCR36 and/or the EGFR37 leading to an increase in [Ca2+]i, and activation of PLC to hydrolyse PIP2, resulting in the release of PIP2-bound p-gelsolin which undergoes dephosphorylation/activation by tyrosine-phosphatase, leading to F-actin dispersion in the head and the occurrence of the AR.


Regulation of Sperm Capacitation and the Acrosome Reaction by PIP 2 and Actin Modulation.

Breitbart H, Finkelstein M - Asian J. Androl. (2015 Jul-Aug)

A model describing the biochemical cascade that leads to the acrosome reaction (AR): the binding of capacitated spermatozoa to the egg zona pellucida causes a fast and high increase in intra-spermatozoal Ca2+ concentration. As a result, active PLC catalyses PIP2 hydrolysis to produce IP3 and diacylglycerol (DAG) and the release of bound p-gelsolin. The p-gelsolin undergoes dephosphorylation/activation by tyrosine phosphatase leadin to conversion of F-actin to G-actin. IP3 activates Ca2+ channel in the outer acrosomal membrane which reduces intra-acrosomal Ca2+ leading to the activation of Ca2+- dependent-Ca2+ channel in the plasma membrane which causes further increase in intracellular Ca2+ which together with DAG activate PKC which mediates the acrosome reaction. Also, PKA-dependent PI3K activation occurs towards the end of the capacitation process, involves in the mechanism leding to the AR.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492050&req=5

Figure 5: A model describing the biochemical cascade that leads to the acrosome reaction (AR): the binding of capacitated spermatozoa to the egg zona pellucida causes a fast and high increase in intra-spermatozoal Ca2+ concentration. As a result, active PLC catalyses PIP2 hydrolysis to produce IP3 and diacylglycerol (DAG) and the release of bound p-gelsolin. The p-gelsolin undergoes dephosphorylation/activation by tyrosine phosphatase leadin to conversion of F-actin to G-actin. IP3 activates Ca2+ channel in the outer acrosomal membrane which reduces intra-acrosomal Ca2+ leading to the activation of Ca2+- dependent-Ca2+ channel in the plasma membrane which causes further increase in intracellular Ca2+ which together with DAG activate PKC which mediates the acrosome reaction. Also, PKA-dependent PI3K activation occurs towards the end of the capacitation process, involves in the mechanism leding to the AR.
Mentions: In conclusion, our data suggest the following model (Figures 4 and 5): the relatively small increase in [Ca2+]i during capacitation leads to conformational changes in gelsolin revealing the F-actin binding site. This change and the increase in F-actin and PIP2 in the sperm head, result in gelsolin being translocated to this region of the cell. Nevertheless, the elevation of PIP2 levels and PKA/Src activation, maintain gelsolin in a phosphorylated/inactivated state and actin polymerization occurs. The increase in F-actin in the tail leads to the development of hyper-activated motility as part of the capacitation process. Immediately prior to the AR (Figure 5), the egg zona-pellucida activates GPCR36 and/or the EGFR37 leading to an increase in [Ca2+]i, and activation of PLC to hydrolyse PIP2, resulting in the release of PIP2-bound p-gelsolin which undergoes dephosphorylation/activation by tyrosine-phosphatase, leading to F-actin dispersion in the head and the occurrence of the AR.

Bottom Line: Stimulation of phospholipase C, by Ca 2 + -ionophore or by activating the epidermal-growth-factor-receptor, inhibits tyrosine phosphorylation of gelsolin and enhances enzyme activity.In conclusion, these data indicate that the increase of PIP 2 and/or F-actin in the head during capacitation enhances gelsolin translocation to the head.As a result, the decrease of gelsolin in the tail allows the maintenance of high levels of F-actin in this structure, which is essential for the development of HA motility.

View Article: PubMed Central - PubMed

Affiliation: The Mina and Everard Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.

ABSTRACT
Actin polymerization and development of hyperactivated (HA) motility are two processes that take place during sperm capacitation. Actin polymerization occurs during capacitation and prior to the acrosome reaction, fast F-actin breakdown takes place. The increase in F-actin during capacitation depends upon inactivation of the actin severing protein, gelsolin, by its binding to phosphatydilinositol-4, 5-bisphosphate (PIP 2 ) and its phosphorylation on tyrosine-438 by Src. Activation of gelsolin following its release from PIP 2 is known to cause F-actin breakdown and inhibition of sperm motility, which can be restored by adding PIP 2 to the cells. Reduction of PIP 2 synthesis inhibits actin polymerization and motility, while increasing PIP 2 synthesis enhances these activities. Furthermore, sperm demonstrating low motility contained low levels of PIP 2 and F-actin. During capacitation there was an increase in PIP 2 and F-actin levels in the sperm head and a decrease in the tail. In spermatozoa with high motility, gelsolin was mainly localized to the sperm head before capacitation, whereas in low motility sperm, most of the gelsolin was localized to the tail before capacitation and translocated to the head during capacitation. We also showed that phosphorylation of gelsolin on tyrosine-438 depends upon its binding to PIP 2 . Stimulation of phospholipase C, by Ca 2 + -ionophore or by activating the epidermal-growth-factor-receptor, inhibits tyrosine phosphorylation of gelsolin and enhances enzyme activity. In conclusion, these data indicate that the increase of PIP 2 and/or F-actin in the head during capacitation enhances gelsolin translocation to the head. As a result, the decrease of gelsolin in the tail allows the maintenance of high levels of F-actin in this structure, which is essential for the development of HA motility.

No MeSH data available.


Related in: MedlinePlus