Abstract：
Fertilization is a complex process that depends on the fusion of the cell membrane of sperm with that of oocyte, and it involves sperm-oocyte recognition, binding, and fusion, which are mediated by multiple proteins. Among those proteins, IZUMO1 and its receptor JUNO have been identified as essential factors for sperm-oocyte recognition and fusion. However, the interaction between IZUMO1 and JUNO alone does not lead to cell membrane fusion, suggesting the involvement of additional proteins in sperm-oocyte membrane fusion. In this study, we have discovered that a protein called WDR54, which consists of WD-repeat modules, is located on the cell membrane of sperm, as well as on the cell membrane and in the cytoplasm of the oocyte. We have found that WDR54 is involved in sperm-oocyte fertilization. When sperm and oocyte were treated with anti-WDR54 ascites, the in vitro fertilization (IVF) rate significantly decreased. Furthermore, our research has shown that WDR54 interacts with both IZUMO1 and JUNO, and it colocalizes with IZUMO1 on the surface of the sperm head and with JUNO on the oocyte surface. Through structural analysis of the putative complexes of WDR54-IZUMO1 and WDR54-JUNO, we infer that these three proteins could form a complex of JUNO-WDR54-IZUMO1-JUNO (referred to as the \"JWIJ complex\") on the oocyte surface. Our findings suggest that WDR54 is an important factor involved in sperm-oocyte adhesion and fusion. This discovery provides new insight into the mechanisms of mammalian sperm-oocyte adhesion and fusion.
摘要：
受精是一个复杂的过程，依赖于精子细胞膜与卵母细胞细胞膜的融合，它涉及精子-卵母细胞识别，绑定,和融合，由多种蛋白质介导。在这些蛋白质中，IZUMO1及其受体JUNO已被确定为精子-卵母细胞识别和融合的重要因子。然而,单独的IZUMO1和JUNO之间的相互作用不会导致细胞膜融合，提示额外的蛋白质参与精子-卵母细胞膜融合。在这项研究中,我们发现了一种名为WDR54的蛋白质，它由WD重复模块组成，位于精子的细胞膜上，以及卵母细胞的细胞膜和细胞质中。我们发现WDR54参与精子-卵母细胞受精。当精子和卵母细胞用抗WDR54腹水处理时，体外受精(IVF)率明显下降。此外，我们的研究表明，WDR54与IZUMO1和JUNO相互作用，它与精子头部表面的IZUMO1和卵母细胞表面的JUNO共定位。通过对WDR54-IZUMO1和WDR54-JUNO的推定复合物的结构分析，我们推断，这三种蛋白质可以在卵母细胞表面形成JUNO-WDR54-IZUMO1-JUNO复合物（称为“JWIJ复合物”）。我们的发现表明，WDR54是参与精子-卵母细胞粘附和融合的重要因素。这一发现为哺乳动物精子-卵母细胞粘附和融合的机制提供了新的见解。
