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TitleThe core outer junction protein CFAP77 connects A- and B-tubules within doublet microtubules of cilia and flagella.
Journal, issue, pagesPLoS Biol, Vol. 23, Issue 10, Page e3003442, Year 2025
Publish dateOct 21, 2025
AuthorsLan Xia / Guo-Liang Yin / Yu Long / Fei Sun / Bin-Bin Wang / Yun Zhu / Su-Ren Chen /
PubMed AbstractThe assembly and physiological function of cilia and flagella depend on the stable association of A- and B-tubules, which form axonemal doublet microtubules (DMTs). However, the mechanisms underlying ...The assembly and physiological function of cilia and flagella depend on the stable association of A- and B-tubules, which form axonemal doublet microtubules (DMTs). However, the mechanisms underlying the connection of B-tubules to A-tubules to form DMTs in mammalian cilia/flagella are unclear. CFAP77 encodes an outer junction (OJ) protein within DMTs that is conserved across many species and cell types. 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 was used to further resolve the in situ structure of sperm axonemal DMTs directly 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 the OJ protein CFAP77 in axonemal A- and B-tubule connections in mammals but also combines in situ structural biology and knockout mice to reveal the underlying structural/molecular mechanism involved.
External linksPLoS Biol / PubMed:41118442 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution24.0 Å
Structure data

EMDB-63568: CFAP77-KO Mouse Sperm Axoneme DMT
Method: EM (subtomogram averaging) / Resolution: 24.0 Å

Source
  • Mus (mice)

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