Although gamete fusion represents the central event in sexual reproduction, the required protein machinery is poorly defined. In sperm cells, Izumo1 and several Izumo1-associated proteins play an essential role for this process. However, so far, the mechanisms underlying transport and maturation of Izumo1 and its incorporation into high molecular weight complexes are incompletely defined. Here, we provide a detailed characterization of the C11orf94 protein, which we rename Frey, which provides a platform for the assembly of Izumo1 complexes. By retaining Izumo1 in the endoplasmic reticulum, Frey facilitates its incorporation into high molecular weight complexes. To fulfill its function, the unstable Frey protein is stabilized within the catalytic center of an intramembrane protease. Loss of Frey results in reduced assembly of Izumo1 complexes and male infertility due to impaired gamete fusion. Collectively, these findings provide mechanistic insights into the early biogenesis and functional relevance of Izumo1 complexes.

中文翻译：

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C11orf94/Frey 是通过控制 Izumo1 复合体组装来调节男性生育能力的关键

尽管配子融合代表了有性生殖的核心事件，但所需的蛋白质机制尚不清楚。在精子细胞中，Izumo1 和几种 Izumo1 相关蛋白在此过程中起着至关重要的作用。然而，到目前为止，Izumo1 的运输和成熟及其掺入高分子量复合物的机制尚未完全确定。在这里，我们提供了 C11orf94 蛋白的详细特征，我们将其重命名为 Frey，它为 Izumo1 复合物的组装提供了一个平台。通过在内质网中保留 Izumo1，Frey 促进其掺入高分子量复合物。为了实现其功能，不稳定的 Frey 蛋白被稳定在膜内蛋白酶的催化中心内。由于配子融合受损，Frey 的缺失导致 Izumo1 复合物的组装减少和男性不育。总的来说，这些发现提供了对 Izumo1 复合物的早期生物发生和功能相关性的机制见解。