School of Environmental and Life Sciences, Discipline of Biological Sciences, The University of Newcastle, University Drive, Callaghan, New South Wales 2308, Australia.
J Biol Chem. 2012 Nov 2;287(45):37659-72. doi: 10.1074/jbc.M112.392803. Epub 2012 Sep 12.
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.
哺乳动物精子在受精卵子之前必须完成顶体反应。顶体反应是一种独特的胞吐事件，涉及一系列长时间的膜融合，最终导致膜囊泡的产生和顶体内容物的释放。这一事件需要大量具有融合能力的信号和支架蛋白的协同作用。在这里，我们发现动力蛋白 GTP 酶家族的两个不同成员定位于成熟小鼠生殖细胞的顶体区。动力蛋白 1 和 2 也存在于成熟小鼠精子的顶体周围区域，因此它们很适合调节顶体反应。两种动力蛋白的药理学抑制剂 dynasore 和 Dyngo-4a 阻断了孕酮诱导的体外顶体胞吐作用，但不能阻断钙离子载体 A23187 的作用，并引起体外受精的相应减少。体内用这些抑制剂处理也导致精子显示出降低的顶体反应潜能。孕酮处理后动力蛋白 1 和 2 的磷酸化增加，这也被 dynasore 选择性阻断。基于我们的综合数据，我们提出动力蛋白可能调节小鼠精子顶体胞吐所需的特定膜融合事件。
