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Publication : C11orf94/Frey is a key regulator for male fertility by controlling Izumo1 complex assembly.

First Author  Contreras W Year  2022
Journal  Sci Adv Volume  8
Issue  32 Pages  eabo6049
PubMed ID  35960805 Mgi Jnum  J:328498
Mgi Id  MGI:7332329 Doi  10.1126/sciadv.abo6049
Citation  Contreras W, et al. (2022) C11orf94/Frey is a key regulator for male fertility by controlling Izumo1 complex assembly. Sci Adv 8(32):eabo6049
abstractText  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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