Elucidation of membrane fusion machinery in fertilization

尽管精卵融合在受精过程中具有重要的生物学意义，但这一步骤背后的分子机制仍然很大程度上未知。本研究利用基因工程小鼠，对精卵融合的分子机制进行了深入的研究。在本申请中，我们获得了关于哺乳动物受精的以下两个方面。我们在精子中发现了一个与IZUMO 1相互作用的蛋白。我们建立了一个Ace3破坏的小鼠系，发现IZUMO 1的定位在精子上的一个稍宽的区域中扩散，但消除ACE 3并不导致精子可复性的丧失。利用Izumo1缺陷的精子，我们发现精子有能力通过ZP至少两次。显然，一些在接触ZP之前很久就经历了顶体反应的精子仍然能够穿过ZP和卵。顶体反应的精子不能与ZP结合并失去其识别能力的观点必须重新考虑。

Despite the biological importance of sperm-egg fusion in fertilization, the molecular mechanisms underlying this step remain largely unknown. We focused on elucidating the molecular mechanisms of sperm-egg fusion by using genetically manipulated mice. In this application, we reached to obtain two aspects about mammalian fertilization as follows. We identified an IZUMO1-interacting protein in spermatozoon. We produced an Ace3 disrupted mouse line, and found the localization of IZUMO1 spread in a little wider area on spermatozoa, but the elimination of ACE3 did not result in a loss of sperm fertilizing ability. Utilizing Izumo1-deficient spermatozoa, we found that the spermatozoa had the ability to pass through the ZP at least twice. Apparently, some spermatozoa that had undergone the acrosome reaction long before contact with the ZP remained capable of crossing the ZP and fertilizing eggs. The concept that acrosome-reacted spermatozoa are unable to bind to the ZP and have lost their fertilizing capacity must be reconsidered.