Cfap53 Regulates Mammalian Cilia-Type Motility Patterns Through Differential Localization And Recruitment Of Axonemal Dynein Components

Motile cilia can beat with distinct patterns, but how motility variations are regulated remain obscure. Here, we have studied the role of the coiled-coil protein CFAP53 in the motility of different cilia-types in the mouse. While node (9+0) cilia of Cfap53 mutants were immotile, tracheal and ependymal (9+2) cilia retained motility, albeit with an altered beat pattern. In node cilia, CFAP53 mainly localized at the base (centriolar satellites), whereas it was also present along the entire axoneme in tracheal cilia. CFAP53 associated tightly with microtubules and interacted with axonemal dyneins and TTC25, a dynein docking complex component. TTC25 and outer dynein arms (ODAs) were lost from node cilia, but were largely maintained in tracheal cilia of Cfap53(-/-) mice. Thus, CFAP53 at the base of node cilia facilitates axonemal transport of TTC25 and dyneins, while axonemal CFAP53 in 9+2 cilia stabilizes dynein binding to microtubules. Our study establishes how differential localization and function of CFAP53 contributes to the unique motion patterns of two important mammalian cilia-types.Author summaryMotile cilia in various kinds of tissues and cell-types drive fluid flow over epithelia or facilitate cellular locomotion. There are two types of motile cilia. Motile cilia with a 9+2 configuration of microtubules are found on tracheal epithelial cells and brain ependymal cells, and exhibit planar beating with effective and recovery strokes. On the other hand, 9+0 motile cilia are found in the embryonic node, show rotational movement and are involved in establishing left-right asymmetry of visceral organs. However, it is not well understood how these two types of motile cilia exhibit their characteristic motion patterns. We have uncovered distinct roles and subcellular localization of the CFAP53 protein in 9+0 versus the 9+2 motile cilia of the mouse. Our data provide novel insights into the molecular basis of motility differences that characterize these two types of mammalian motile cilia.