title: CaMKII prevents spontaneous acrosomal exocytosis in sperm through induction of actin polymerization.
abstract: In order to interact with the egg and undergo acrosomal exocytosis or the acrosome reaction (AR), mammalian spermatozoa must undergo a series of biochemical changes in the female reproductive tract, collectively called capacitation. We showed that F-actin is formed during sperm capacitation and fast depolymerization occurs prior to the AR. We hypothesized that F-actin protects the sperm from undergoing spontaneous-AR (sAR) which decreases fertilization rate. We show that activation of the actin-severing protein gelsolin induces a significant increase in sAR. Moreover, inhibition of CaMKII or PLD during sperm capacitation, caused an increase in sAR and inhibition of F-actin formation. Spermine, which leads to PLD activation, was able to reverse the effects of CaMKII inhibition on sAR-increase and F-actin-decrease. Furthermore, the increase in sAR and the decrease in F-actin caused by the inactivation of the PLD-pathway, were reversed by activation of CaMKII using H2O2 or by inhibiting protein phosphatase 1 which enhance the phosphorylation and oxidation states of CaMKII. These results indicate that two distinct pathways lead to F-actin formation in the sperm capacitation process which prevents the occurrence of sAR.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Ortal
authors.initials: O
authors.lastname: Shabtay
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel. Electronic address: Haim.breitbart@biu.ac.il.
authors.forename: Haim
authors.initials: H
authors.lastname: Breitbart
mesh_terms: D000177:Acrosome / Q000201:enzymology*; D020101:Acrosome Reaction / Q000502:physiology*; D008841:Actin Cytoskeleton / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002417:Cattle; D004789:Enzyme Activation / Q000187:drug effects; D005089:Exocytosis / Q000502:physiology; D018260:Gelsolin / Q000378:metabolism / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D008387:Marine Toxins; D010080:Oxazoles / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000502:physiology; D058105:Polymerization; D013075:Sperm Capacitation / Q000502:physiology; D013094:Spermatozoa / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D000199:Actins; D018260:Gelsolin; D008387:Marine Toxins; D010080:Oxazoles; D010446:Peptide Fragments; C527698:gelsolin (160-169); D000001:Calcimycin; C059041:calyculin A; D006861:Hydrogen Peroxide; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D010739:Phospholipase D
keywords: Acrosome reaction; Actin; CaMKII; PLD; ROS; Spermatozoa