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TitleLRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility.
Journal, issue, pagesElife, Vol. 12, Year 2023
Publish dateDec 13, 2023
AuthorsJae Yeon Hwang / Pengxin Chai / Shoaib Nawaz / Jungmin Choi / Francesc Lopez-Giraldez / Shabir Hussain / Kaya Bilguvar / Shrikant Mane / Richard P Lifton / Wasim Ahmad / Kai Zhang / Jean-Ju Chung /
PubMed AbstractRadial spokes (RS) are T-shaped multiprotein complexes on the axonemal microtubules. Repeated RS1, RS2, and RS3 couple the central pair to modulate ciliary and flagellar motility. Despite the cell ...Radial spokes (RS) are T-shaped multiprotein complexes on the axonemal microtubules. Repeated RS1, RS2, and RS3 couple the central pair to modulate ciliary and flagellar motility. Despite the cell type specificity of RS3 substructures, their molecular components remain largely unknown. Here, we report that a leucine-rich repeat-containing protein, LRRC23, is an RS3 head component essential for its head assembly and flagellar motility in mammalian spermatozoa. From infertile male patients with defective sperm motility, we identified a splice site variant of . A mutant mouse model mimicking this variant produces a truncated LRRC23 at the C-terminus that fails to localize to the sperm tail, causing male infertility due to defective sperm motility. LRRC23 was previously proposed to be an ortholog of the RS stalk protein RSP15. However, we found that purified recombinant LRRC23 interacts with an RS head protein RSPH9, which is abolished by the C-terminal truncation. Evolutionary and structural comparison also shows that LRRC34, not LRRC23, is the RSP15 ortholog. Cryo-electron tomography clearly revealed that the absence of the RS3 head and the sperm-specific RS2-RS3 bridge structure in LRRC23 mutant spermatozoa. Our study provides new insights into the structure and function of RS3 in mammalian spermatozoa and the molecular pathogenicity of LRRC23 underlying reduced sperm motility in infertile human males.
External linksElife / PubMed:38091523 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution27.0 - 34.0 Å
Structure data

EMDB-28606: 96nm doublet microtubule repeat from LRRC23-KO mouse sperm
Method: EM (subtomogram averaging) / Resolution: 27.0 Å

EMDB-29013: 96nm doublet microtubule repeat from wild type mouse sperm
Method: EM (subtomogram averaging) / Resolution: 34.0 Å

Source
  • Mus (mice)

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