CFAP53 regulates mammalian cilia-type motility patterns through differential localization and recruitment of axonemal dynein components.

Takahiro Ide,Katsuyoshi Takaoka,Hiromi Nishimura,Nicole Henninger,Yayoi Ikawa,Xiumin Yan,Hidetaka Shiratori,Lin-Xenia Lim,Sudipto Roy,Wang Kyaw Twan,Hao Lu,Hiroshi Hamada,Vijay Narasimhan,Susan K Dutcher

doi:10.1371/journal.pgen.1009232

Abstract

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.

Highlights

Cilia are widely found in diverse animals, ranging from protozoans to man
Motile cilia with a 9+2 configuration of microtubules are found on tracheal epithelial cells and brain ependymal
Assembled complexes are transported to the basal body, and into the axoneme by intraflagellar transport (IFT), and docked to microtubules through the docking complex (DC) composed of TTC25 [11], CCDC114 [12], CCDC151 [13] and ARMC4 [14]

Summary

Introduction

Cilia are widely found in diverse animals, ranging from protozoans to man. Many of them are immotile, but some of them, such as those found in the mammalian trachea, brain ventricle, reproductive organs and male gametes are motile [1]. Motor proteins that directly generate the force for ciliary motility, form multisubunit ATPase complexes as outer and inner dynein arms (ODAs and IDAs, respectively) attached to the peripheral doublet microtubules of the cilium. Additional accessory structures, such as radial spokes and nexin links, are involved in the regulation of dynein activity. Many of the genes involved in these steps have been discovered by studying various model organisms and through the identification of causative mutations in human ciliary diseases, the full mechanism remains far from being completely understood

Methods

Results

Conclusion