
FBXO24は精子鞭毛の形成と機能維持に必須であり、その欠失により膜レス顆粒が異常に蓄積し、精子運動性の低下と男性不妊を引き起こす。


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Ribonucleoprotein (RNP) granules are membraneless electron-dense structures rich in RNAs and proteins, and involved in various cellular processes. Two RNP granules in male germ cells, intermitochondrial cement and the chromatoid body (CB), are associated with PIWI-interacting RNAs (piRNAs) and are required for transposon silencing and spermatogenesis. Other RNP granules in male germ cells, the reticulated body and CB remnants, are also essential for spermiogenesis. In this study, we disrupted FBXO24, a testis-enriched F-box protein, in mice and found numerous membraneless electron-dense granules accumulated in sperm flagella. Fbxo24 knockout (KO) mice exhibited malformed flagellar structures, impaired sperm motility, and male infertility, likely due to the accumulation of abnormal granules. The amount and localization of known RNP granule-related proteins were not disrupted in Fbxo24 KO mice, suggesting that the accumulated granules were distinct from known RNP granules. Further studies revealed that RNAs and two importins, IPO5 and KPNB1, abnormally accumulated in Fbxo24 KO spermatozoa and that FBXO24 could ubiquitinate IPO5. In addition, IPO5 and KPNB1 were recruited to stress granules, RNP complexes, when cells were treated with oxidative stress or a proteasome inhibitor. These results suggest that FBXO24 is involved in the degradation of IPO5, disruption of which may lead to the accumulation of abnormal RNP granules in sperm flagella.

### Competing Interest Statement

The authors have declared no competing interest.

FBXO24 deletion causes abnormal accumulation of membraneless electron-dense granules in sperm flagella and male infertility

精子鞭毛の異常な膜レス顆粒の蓄積を防ぐことで男性不妊を防ぐfbxo24


精子鞭毛の異常な膜レス顆粒の蓄積を防ぐことで男性不妊を防ぐFBXO24
