Calaxin stabilizes the docking of outer arm dyneins onto ciliary doublet microtubule in vertebrates.

Yamaguchi, Hiroshi; Morikawa, Motohiro; Kikkawa, Masahide · Elife · 2023

basic_science · Level V

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Abstract

Outer arm dynein (OAD) is the main force generator of ciliary beating. Although OAD loss is the most frequent cause of human primary ciliary dyskinesia, the docking mechanism of OAD onto the ciliary doublet microtubule (DMT) remains elusive in vertebrates. Here, we analyzed the functions of Calaxin/Efcab1 and Armc4, the two of five components of vertebrate OAD-DC (docking complex), using zebrafish spermatozoa and cryo-electron tomography. Mutation of <i>armc4</i> caused complete loss of OAD, whereas mutation of <i>calaxin</i> caused only partial loss of OAD. Detailed structural analysis revealed that <i>calaxin</i><sup>-/-</sup> OADs are tethered to DMT through DC components other than Calaxin, and that recombinant Calaxin can autonomously rescue the deficient DC structure and the OAD instability. Our data demonstrate the discrete roles of Calaxin and Armc4 in the OAD-DMT interaction, suggesting the stabilizing process of OAD docking onto DMT in vertebrates.

Medical subject headings