Department of Biology, Technion - Israel Institute of Technology, Haifa, Israel.
Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Aichi, Japan.
J Cell Biol. 2023 Feb 6;222(2). doi: 10.1083/jcb.202207147. Epub 2022 Nov 17.
Mammalian sperm-egg adhesion depends on the trans-interaction between the sperm-specific type I glycoprotein IZUMO1 and its oocyte-specific GPI-anchored receptor JUNO. However, the mechanisms and proteins (fusogens) that mediate the following step of gamete fusion remain unknown. Using live imaging and content mixing assays in a heterologous system and structure-guided mutagenesis, we unveil an unexpected function for IZUMO1 in cell-to-cell fusion. We show that IZUMO1 alone is sufficient to induce fusion, and that this ability is retained in a mutant unable to bind JUNO. On the other hand, a triple mutation in exposed aromatic residues prevents this fusogenic activity without impairing JUNO interaction. Our findings suggest a second function for IZUMO1 as a unilateral mouse gamete fusogen.
哺乳动物精卵黏附依赖于精子特异性的 I 型糖蛋白 IZUMO1 与其卵母细胞特异性的 GPI 锚定受体 JUNO 之间的跨相互作用。然而，介导随后的配子融合的机制和蛋白质（融合蛋白）仍然未知。通过在异源系统中的活细胞成像和内容混合测定以及结构导向的突变，我们揭示了 IZUMO1 在细胞间融合中的一个意外功能。我们表明，IZUMO1 本身足以诱导融合，并且这种能力在不能结合 JUNO 的突变体中保留。另一方面，暴露的芳香族残基的三突变阻止了这种融合活性，而不损害 JUNO 相互作用。我们的研究结果表明，IZUMO1 作为一种单侧鼠配子融合蛋白具有第二个功能。
