title: Regulation of Sperm Capacitation and the Acrosome Reaction by PIP 2 and Actin Modulation.
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.
authors.affiliation: The Mina and Everard Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Haim
authors.initials: H
authors.lastname: Breitbart
authors.forename: Maya
authors.initials: M
authors.lastname: Finkelstein
mesh_terms: D020101:Acrosome Reaction / Q000502:physiology*; D000199:Actins / Q000235:genetics / Q000502:physiology*; D018260:Gelsolin / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000235:genetics / Q000502:physiology*; D013075:Sperm Capacitation / Q000502:physiology*
chemical_list: D000199:Actins; D018260:Gelsolin; D019269:Phosphatidylinositol 4,5-Diphosphate