Inoue Naokazu, Hagihara Yoshihisa, Wright Danelle, Suzuki Takahisa, Wada Ikuo
Department of Cell Science, Institutes for Biomedical Sciences, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima City, Fukushima 960-1295, Japan.
National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan.
Nat Commun. 2015 Nov 16;6:8858. doi: 10.1038/ncomms9858.
Sperm-egg fusion is indispensable for completing mammalian fertilization. Although the underlying molecular mechanisms are poorly understood, requirement of two spermatozoon factors, IZUMO1 and SPACA6, and two oocyte factors, CD9 and the IZUMO1 counter-receptor JUNO, has been proven by gene disruption, and the binding of cells to an oocyte can be reconstituted by ectopic expression of IZUMO1. Here we demonstrate that robust IZUMO1-dependent adhesion of sperm with an oocyte accompanies the dimerization of IZUMO1. Despite the intrinsic dimeric property of its N-terminal region, IZUMO1 is monomeric in spermatozoa. Interestingly, JUNO associates with monomeric IZUMO1, which is then quickly removed as tight adhesion of the two cells is subsequently established. We therefore propose that global structural rearrangement of IZUMO1 occurs on JUNO recognition and that this rearrangement may then initiate force generation to overcome repulsion between the juxtaposing membranes, through an unidentified receptor on the egg.
精卵融合对于完成哺乳动物受精过程不可或缺。尽管其潜在的分子机制尚不清楚，但通过基因敲除已证实了两种精子因子IZUMO1和SPACA6以及两种卵母细胞因子CD9和IZUMO1的反受体JUNO的必要性，并且通过IZUMO1的异位表达可以重建细胞与卵母细胞的结合。在此，我们证明精子与卵母细胞之间强大的依赖IZUMO1的黏附伴随着IZUMO1的二聚化。尽管IZUMO1的N端区域具有内在的二聚体特性，但它在精子中是单体形式。有趣的是，JUNO与单体IZUMO1结合，随后随着两个细胞紧密黏附的建立，JUNO会迅速被移除。因此，我们提出IZUMO1的整体结构重排在与JUNO识别时发生，并且这种重排可能随后通过卵上未知的受体引发力的产生，以克服并列膜之间的排斥力。
