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bioRxiv · 10.1101/2025.02.23.639767

Essential role of CFAP77-CCDC105-TEX43 subcomplex in connecting axonemal A and B tubules for mammalian sperm motility

Xia, L.·Yin, G.-L.·Long, Y.·Sun, F.·Wang, B.-B.·Zhu, Y.·Chen, S.-R.
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Abstract

The assembly and physiological function of cilia and flagella depend on the stable association of A and B tubules, which form axonemal microtubule doublets (DMTs). CFAP77 encodes a core outer junction (OJ) protein within DMTs that is conserved across species and cell types. However, whether and how CFAP77 mediates the connection of B tubules to A tubules of DMTs in mammalian cilia/flagella are unknown. In this study, Cfap77-KO mice were generated to reveal that CFAP77 is essential for sperm progressive motility and male fertility. Loss of CFAP77 led to opened B tubules specifically at the OJ regions of axonemal DMTs as revealed by conventional transmission electron microscopy. Cryo-electron tomography further resolved the in situ structure of sperm axonemal DMTs from Cfap77-KO mice, which exhibited a loss of large filamentous density corresponding to the CFAP77-CCDC105-TEX43 ternary subcomplex at the OJ regions. Additionally, sperm proteomic analysis confirmed that CFAP77 knockout led to the complete loss of this ternary complex. Our work not only explores the physiological role of OJ protein CFAP77 on axonemal A-B tubule connection in mammals but also combines in situ structural biology and knockout mice to reveal the underlying structural/molecular mechanism.

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Xia, L., Yin, G.-L., Long, Y., Sun, F., Wang, B.-B., Zhu, Y., Chen, S.-R.. 2025-02-25. Essential role of CFAP77-CCDC105-TEX43 subcomplex in connecting axonemal A and B tubules for mammalian sperm motility. https://doi.org/10.1101/2025.02.23.639767

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