Ccdc113/Ccdc96 complex, a novel regulator of ciliary beating that connects radial spoke 3 to dynein g and the nexin link.

Rafał Bazan,Dorota Wloga,Martyna Poprzeczko,Adam Schröfel,Ewa Joachimiak,Gaia Pigino,Chad Pearson

doi:10.1371/journal.pgen.1009388

Abstract

Ciliary beating requires the coordinated activity of numerous axonemal complexes. The protein composition and role of radial spokes (RS), nexin links (N-DRC) and dyneins (ODAs and IDAs) is well established. However, how information is transmitted from the central apparatus to the RS and across other ciliary structures remains unclear. Here, we identify a complex comprising the evolutionarily conserved proteins Ccdc96 and Ccdc113, positioned parallel to N-DRC and forming a connection between RS3, dynein g, and N-DRC. Although Ccdc96 and Ccdc113 can be transported to cilia independently, their stable docking and function requires the presence of both proteins. Deletion of either CCDC113 or CCDC96 alters cilia beating frequency, amplitude and waveform. We propose that the Ccdc113/Ccdc96 complex transmits signals from RS3 and N-DRC to dynein g and thus regulates its activity and the ciliary beat pattern.

Highlights

Motile cilia and flagella are microtubule-based cell protrusions that are indispensable for the development and physiology of eukaryotic organisms from a wide range of evolutionary lineages, including humans
There are four outer dynein arms (ODAs) that are generally identical in their protein composition and function, seven inner dynein arms (IDAs) that differ in their architecture and protein subunits, three radial spokes (RSs), and one nexin-dynein regulatory complex (N-DRC)
To provide novel insights into how the N-DRC contributes to the coordination of axonemal complexes activity, we searched for additional, as-yet unidentified N-DRC components or connectors

Summary

Introduction

Motile cilia and flagella are microtubule-based cell protrusions that are indispensable for the development and physiology of eukaryotic organisms from a wide range of evolutionary lineages, including humans. Cryo-electron microscopy analyses of the axoneme have shown that besides the main complexes, the axonemal unit contains numerous minor structures, mostly of unknown protein composition and function [2,4,10,12,14,15]. The activity of these axonemal complexes has to be strictly coordinated locally within the axonemal unit and globally, both circumferentially and longitudinally along the axoneme, in order for it to be translated into normal ciliary beating [17].

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Conclusion