Contreras Whendy, Wiesehöfer Caroline, Schreier Dora, Leinung Nadja, Peche Petra, Wennemuth Gunther, Gentzel Marc, Schröder Bernd, Mentrup Torben
Institute of Physiological Chemistry, Technische Universität Dresden, Dresden, Germany.
Department of Anatomy, University Hospital, University of Duisburg-Essen, Essen, Germany.
Sci Adv. 2022 Aug 12;8(32):eabo6049. doi: 10.1126/sciadv.abo6049.
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.
尽管配子融合是有性生殖的核心事件，但所需的蛋白质机制仍不清楚。在精子细胞中，Izumo1和几种与Izumo1相关的蛋白质在这一过程中起着至关重要的作用。然而，到目前为止，Izumo1的运输和成熟及其整合到高分子量复合物中的潜在机制尚未完全明确。在这里，我们对C11orf94蛋白进行了详细的表征，我们将其重新命名为Frey，它为Izumo1复合物的组装提供了一个平台。通过将Izumo1保留在内质网中，Frey促进其整合到高分子量复合物中。为了发挥其功能，不稳定的Frey蛋白在内膜蛋白酶的催化中心内得到稳定。Frey的缺失导致Izumo1复合物组装减少，并因配子融合受损而导致雄性不育。总的来说，这些发现为Izumo1复合物的早期生物发生和功能相关性提供了机制上的见解。
