期刊
SCIENCE ADVANCES
卷 8, 期 32, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abo6049
关键词
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资金
- German Federal Ministry of Education and Research (BMBF) program Unternehmen Region [03Z2ES1, 03Z22EB1]
- German Research Foundation [ME 5459/1-1, INST 269/731-1 FUGG, SFB877, WE 2344/9-3, SCHR 1284/2-1, SCHR1284/1-2]
- European Regional Development Fund (ERDF/EFRE) [100232736]
- MeDDrive Grant from the Medical Faculty Carl Gustav Carus of the Technische Universitat Dresden
This study provides a detailed characterization of the C11orf94 protein, renamed as Frey, which plays a crucial role in the assembly of Izumo1 complexes. By retaining Izumo1 in the endoplasmic reticulum, Frey facilitates its incorporation into high molecular weight complexes.
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.
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