Lrrcc1 and Ccdc61 are conserved effectors of multiciliated cell function
Aude Nommick, Camille Boutin, Olivier Rosnet, Claire Schirmer, Elsa Bazellières, Virginie Thomé, Étienne Loiseau, Annie Viallat, Laurent Kodjabachian
Abstract
Ciliated epithelia perform essential functions in animals across evolution, ranging from locomotion of marine organisms to mucociliary clearance of airways in mammals. These epithelia are composed of multiciliated cells (MCCs) harboring myriads of motile cilia, which rest on modified centrioles called basal bodies (BBs), and beat coordinately to generate directed fluid flows. Thus, BB biogenesis and organization is central to MCC function. In basal eukaryotes, the coiled-coil domain proteins Lrrcc1 and Ccdc61 have previously been shown to be required for proper BB construction and function. Here, we used the Xenopus embryonic ciliated epidermis to characterize Lrrcc1 and Ccdc61 in vertebrate MCCs. We found that they both encode BB components, localized proximally at the junction with striated rootlets. Knocking down either gene caused defects in BB docking, spacing and polarization. Moreover, their depletion impaired the apical cytoskeleton and altered ciliary beating. Consequently, cilia-powered fluid flow was greatly reduced in morphant tadpoles, which displayed enhanced mortality when exposed to pathogenic bacteria. This work illustrates how integration across organizational scales make elementary BB components essential for the emergence of the physiological function of ciliated epithelia.