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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: During capacitation there was an increase in PIP 2 and F-actin levels in the sperm head and a decrease in the tail.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.


PIP2 and phopholiase C mediate actin modulation: binding of gelsolin to PIP2 causes its inactivation. Activation of PLCγ by the epidermal-grwth-factor-receptor (EGFR) leads to PIP2 hydrolysis and the release of bound gelsolin, which activates and causes F-actin depolymerization.
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Figure 2: PIP2 and phopholiase C mediate actin modulation: binding of gelsolin to PIP2 causes its inactivation. Activation of PLCγ by the epidermal-grwth-factor-receptor (EGFR) leads to PIP2 hydrolysis and the release of bound gelsolin, which activates and causes F-actin depolymerization.

Mentions: Gelsolin activation is regulated by calcium ions, phosphoinositides182425 and by Src-dependent phosphorylation on tyr-438.26 Low concentration of calcium ions cause conformational changes in the C-terminus of gelsolin, which expose its F-actin binding site while higher calcium levels cause a second conformational change exposing the catalytic site.27 In human spermatozoa, activation of gelsolin by enhancing intracellular calcium concentration or by using the peptide PBP10 causes fast depolymerization of F-actin and induction of the AR in capacitated sperm.22 In Sertoli cells, the hydrolysis of PIP2 by PLC resulted in the release the bound gelsolin and its activation.28 A scheme describing the physiological activation of PLC is seen in Figure 2. It is well known that activation of EGFR by EGF or elevation of intra-spermatozoal [Ca2+] using Ca2+-ionophore activates PLCγ.22 In Table 2 we show that EGF or Ca2+-ionophore induces fast F-actin depolymerization and the AR while both are blocked by inhibiting PLC. The induction of F-actin breakdown or AR by PBP10 is not affected by inhibiting PLC, indicating the specificity of PLC inhibition to PIP2 hydrolysis.


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

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

PIP2 and phopholiase C mediate actin modulation: binding of gelsolin to PIP2 causes its inactivation. Activation of PLCγ by the epidermal-grwth-factor-receptor (EGFR) leads to PIP2 hydrolysis and the release of bound gelsolin, which activates and causes F-actin depolymerization.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: PIP2 and phopholiase C mediate actin modulation: binding of gelsolin to PIP2 causes its inactivation. Activation of PLCγ by the epidermal-grwth-factor-receptor (EGFR) leads to PIP2 hydrolysis and the release of bound gelsolin, which activates and causes F-actin depolymerization.
Mentions: Gelsolin activation is regulated by calcium ions, phosphoinositides182425 and by Src-dependent phosphorylation on tyr-438.26 Low concentration of calcium ions cause conformational changes in the C-terminus of gelsolin, which expose its F-actin binding site while higher calcium levels cause a second conformational change exposing the catalytic site.27 In human spermatozoa, activation of gelsolin by enhancing intracellular calcium concentration or by using the peptide PBP10 causes fast depolymerization of F-actin and induction of the AR in capacitated sperm.22 In Sertoli cells, the hydrolysis of PIP2 by PLC resulted in the release the bound gelsolin and its activation.28 A scheme describing the physiological activation of PLC is seen in Figure 2. It is well known that activation of EGFR by EGF or elevation of intra-spermatozoal [Ca2+] using Ca2+-ionophore activates PLCγ.22 In Table 2 we show that EGF or Ca2+-ionophore induces fast F-actin depolymerization and the AR while both are blocked by inhibiting PLC. The induction of F-actin breakdown or AR by PBP10 is not affected by inhibiting PLC, indicating the specificity of PLC inhibition to PIP2 hydrolysis.

Bottom Line: During capacitation there was an increase in PIP 2 and F-actin levels in the sperm head and a decrease in the tail.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.