Oocyte-triggered dimerization of sperm IZUMO1 promotes sperm-egg fusion in mice.
Oocyte-triggered dimerization of sperm IZUMO1 promotes sperm-egg fusion in mice.
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DOI：
10.1038/ncomms9858
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发表时间：
2015-11-16
影响因子：
16.6
通讯作者：
Wada I
中科院分区：
文献类型：
--
作者：
Inoue N;Hagihara Y;Wright D;Suzuki T;Wada I
精卵融合对于完成哺乳动物受精是必不可少的。尽管人们对潜在的分子机制知之甚少，但基因破坏已经证明了对两种精子因子 IZUMO1 和 SPACA6 以及两种卵母细胞因子 CD9 和 IZUMO1 反受体 JUNO 的需求，并且细胞与卵母细胞的结合可以通过 IZUMO1 的异位表达来重建。在这里，我们证明了精子与卵母细胞之间强大的 IZUMO1 依赖性粘附伴随着 IZUMO1 的二聚化。尽管 IZUMO1 N 端区域具有固有的二聚体特性，但 IZUMO1 在精子中是单体。有趣的是，JUNO 与单体 IZUMO1 结合，随后随着两个细胞建立紧密粘附，单体 IZUMO1 很快被移除。因此，我们提出 IZUMO1 的整体结构重排发生在 JUNO 识别时，并且这种重排可能随后通过卵上的未识别受体启动力的产生，以克服并置膜之间的排斥力。 精子特异性受体 IZUMO1 和卵子特异性反受体 JUNO 促进精卵融合。这里 Inoue 等人。表明 JUNO 首先与单体 IZUMO1 结合；然后 IZUMO1 二聚化并将 JUNO 排除在精卵界面之外，表明 IZUMO1 二聚体受体的存在。
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. Sperm-egg fusion is facilitated by the sperm-specific receptor IZUMO1 and the egg-specific counter-receptor JUNO. Here Inoue et al. show that JUNO first binds to monomeric IZUMO1; IZUMO1 then dimerizes and excludes JUNO from the sperm-egg interface, suggesting the existence of a IZUMO1 dimer receptor.