LRRC23 is a conserved component of the radial spoke that is necessary for sperm motility and male fertility in mice

Zhang, X.; Sun, J.; Lu, Y.; Zhang, J.; Shimada, K.; Noda, T.; Zhao, S.; Koyano, T.; Matsuyama, M.; Zhou, S.; Wu, J.; Ikawa, M.; Liu, M.

doi:10.1101/2021.06.01.446532

bioRxiv · 10.1101/2021.06.01.446532

LRRC23 is a conserved component of the radial spoke that is necessary for sperm motility and male fertility in mice

Zhang, X.·Sun, J.·Lu, Y.·Zhang, J.·Shimada, K.·Noda, T.·Zhao, S.·Koyano, T.·Matsuyama, M.·Zhou, S.·Wu, J.·Ikawa, M.·Liu, M.

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Abstract

Cilia and flagella are ancient structures that achieve controlled motor functions through the coordinated interaction of structures including dynein arms, radial spokes (RSs), microtubules, and the dynein regulatory complex (DRC). RSs facilitate the beating motion of these organelles by mediating signal transduction between dyneins and a central pair (CP) of singlet microtubules. RS complex isolation from Chlamydomonas axonemes enabled the detection of 23 different proteins (RSP1-23), with the roles of RSP13, RSP15, RSP18, RSP19, and RSP21 remained poorly understood. Herein, we show that Lrrc23 is an evolutionarily conserved testis-enriched gene encoding an RSP15 homolog in mice. Through immunoelectron microscopy, we demonstrate that LRRC23 localizes to the RS complex within murine sperm flagella. We further found that LRRC23 was able to interact with RSHP9 and RSPH3A/B. The knockout of Lrrc23 resulted in RS disorganization and impaired motility in murine spermatozoa, whereas the ciliary beating was unaffected by the loss of this protein. Spermatozoa lacking LRRC23 were unable to efficiently pass through the uterotubal junction and exhibited defective zona penetration. Together these data indicate that LRRC23 is a key regulator underpinning the integrity of RS complex within the flagella of mammalian spermatozoa, whereas it is dispensable in cilia. Author summary

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Zhang, X., Sun, J., Lu, Y., Zhang, J., Shimada, K., Noda, T., Zhao, S., Koyano, T., Matsuyama, M., Zhou, S., Wu, J., Ikawa, M., Liu, M.. 2021-06-01. LRRC23 is a conserved component of the radial spoke that is necessary for sperm motility and male fertility in mice. https://doi.org/10.1101/2021.06.01.446532

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