Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
Mouse Production Team, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
Nature. 2014 Apr 24;508(7497):483-7. doi: 10.1038/nature13203. Epub 2014 Apr 16.
Fertilization occurs when sperm and egg recognize each other and fuse to form a new, genetically distinct organism. The molecular basis of sperm-egg recognition is unknown, but is likely to require interactions between receptor proteins displayed on their surface. Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. Here we identify folate receptor 4 (Folr4) as the receptor for Izumo1 on the mouse egg, and propose to rename it Juno. We show that the Izumo1-Juno interaction is conserved within several mammalian species, including humans. Female mice lacking Juno are infertile and Juno-deficient eggs do not fuse with normal sperm. Rapid shedding of Juno from the oolemma after fertilization suggests a mechanism for the membrane block to polyspermy, ensuring eggs normally fuse with just a single sperm. Our discovery of an essential receptor pair at the nexus of conception provides opportunities for the rational development of new fertility treatments and contraceptives.
受精发生在精子和卵子识别并融合形成新的、具有独特遗传特征的生物体时。精子-卵子识别的分子基础尚不清楚，但可能需要受体蛋白在其表面的相互作用。Izumo1 是一种必需的精子细胞表面蛋白，但它在卵子上的受体尚未被描述。在这里，我们确定叶酸受体 4（Folr4）是小鼠卵子上 Izumo1 的受体，并提议将其重新命名为 Juno。我们表明，Izumo1-Juno 相互作用在包括人类在内的几种哺乳动物物种中是保守的。缺乏 Juno 的雌性小鼠不育，并且 Juno 缺乏的卵子不能与正常精子融合。受精后 Juno 从卵母细胞膜上快速脱落，这表明了阻止多精入卵的一种机制，从而确保卵子通常只与单个精子融合。我们在受孕的关键部位发现了一对必需的受体，这为开发新的生育治疗和避孕方法提供了机会。
