title: Dynamin regulates specific membrane fusion events necessary for acrosomal exocytosis in mouse spermatozoa.
abstract: Mammalian spermatozoa must complete an acrosome reaction prior to fertilizing an oocyte. The acrosome reaction is a unique exocytotic event involving a series of prolonged membrane fusions that ultimately result in the production of membrane vesicles and release of the acrosomal contents. This event requires the concerted action of a large number of fusion-competent signaling and scaffolding proteins. Here we show that two different members of the dynamin GTPase family localize to the developing acrosome of maturing mouse germ cells. Both dynamin 1 and 2 also remain within the periacrosomal region of mature mouse spermatozoa and are thus well positioned to regulate the acrosome reaction. Two pharmacological inhibitors of dynamin, dynasore and Dyngo-4a, blocked the in vitro induction of acrosomal exocytosis by progesterone, but not by the calcium ionophore A23187, and elicited a concomitant reduction of in vitro fertilization. In vivo treatment with these inhibitors also resulted in spermatozoa displaying reduced acrosome reaction potential. Dynamin 1 and 2 phosphorylation increased on progesterone treatment, and this was also selectively blocked by dynasore. On the basis of our collective data, we propose that dynamin could regulate specific membrane fusion events necessary for acrosomal exocytosis in mouse spermatozoa.
authors.affiliation: School of Environmental and Life Sciences, Discipline of Biological Sciences, The University of Newcastle, University Drive, Callaghan, New South Wales 2308, Australia.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Reid
authors.forename: Tessa
authors.initials: T
authors.lastname: Lord
authors.forename: Simone J
authors.initials: SJ
authors.lastname: Stanger
authors.forename: Shaun D
authors.initials: SD
authors.lastname: Roman
authors.forename: Adam
authors.initials: A
authors.lastname: McCluskey
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Robinson
authors.forename: R John
authors.initials: RJ
authors.lastname: Aitken
authors.forename: Brett
authors.initials: B
authors.lastname: Nixon
mesh_terms: D000177:Acrosome / Q000187:drug effects / Q000378:metabolism*; D020101:Acrosome Reaction / Q000187:drug effects; D000818:Animals; D015153:Blotting, Western; D034284:Dynamin I / Q000037:antagonists & inhibitors / Q000378:metabolism; D034285:Dynamin II / Q000037:antagonists & inhibitors / Q000378:metabolism; D034281:Dynamins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005089:Exocytosis; D005260:Female; D005307:Fertilization in Vitro; D006835:Hydrazones / Q000494:pharmacology; D008297:Male; D008561:Membrane Fusion; D051379:Mice; D018613:Microscopy, Confocal; D009284:Naphthols / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000378:metabolism
chemical_list: D006835:Hydrazones; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; D009284:Naphthols; D011372:Progestins; C568360:dyngo-4a; D011374:Progesterone; D034284:Dynamin I; D034285:Dynamin II; D034281:Dynamins