Ciliary Proteins: Filling the Gaps. Recent Advances in Deciphering the Protein Composition of Motile Ciliary Complexes

Abstract

Cilia are highly evolutionarily conserved, microtubule-based cell protrusions present in eukaryotic organisms from protists to humans, with the exception of fungi and higher plants. Cilia can be broadly divided into non-motile sensory cilia, called primary cilia, and motile cilia, which are locomotory organelles. The skeleton (axoneme) of primary cilia is formed by nine outer doublet microtubules distributed on the cilium circumference. In contrast, the skeleton of motile cilia is more complex: in addition to outer doublets, it is composed of two central microtubules and several diverse multi-protein complexes that are distributed periodically along both types of microtubules. For many years, researchers have endeavored to fully characterize the protein composition of ciliary macro-complexes and the molecular basis of signal transduction between these complexes. Genetic and biochemical analyses have suggested that several hundreds of proteins could be involved in the assembly and function of motile cilia. Within the last several years, the combined efforts of researchers using cryo-electron tomography, genetic and biochemical approaches, and diverse model organisms have significantly advanced our knowledge of the ciliary structure and protein composition. Here, we summarize the recent progress in the identification of the subunits of ciliary complexes, their precise intraciliary localization determined by cryo-electron tomography data, and the role of newly identified proteins in cilia.

The FOXJ1 target Cfap206 is required for sperm motility, mucociliary clearance of the airways and brain development

“…However, given the specific function as an adapter for RS2 in Tetrahymena, it seems reasonable to assume that the RS consistently observed at 96 nm distance in mutant mouse sperm is RS1. A RS-related function of CFAP206 is also supported by its absence from the ciliary tip that apparently lacks radial spokes (reviewed by Osinka et al, 2019;Reynolds et al, 2018;Soares et al, 2019) and would be consistent with the lack of laterality defects in mouse and frog, as motile cilia at the LRO lack the central pair and RSs and show a rotational movement (Nonaka et al, 1998). The absence of LR defects is also a characteristic of individuals with PCD with defects in radial spokes and the central pair (Edelbusch et al, 2017;Lucas et al, 2019).…”

Structural insights into the architecture and assembly of eukaryotic flagella

“…Additionally, the architecture of the T-shaped protein radial spoke (RS) complexes that connect DMTs to the central pair MTs has been resolved [ 47 ]. ODA, IDA, RS and N-DRC axonemal structures have been comprehensively reviewed by others [ 4 , 56 , 57 ] and will not be further covered here.…”

Sperm defects in primary ciliary dyskinesia and related causes of male infertility

“…1c) The N-DRC regulates and coordinates the activity of the dynein arms [43]. The current knowledge of motile cilia ultrastructure and protein content has been previously reviewed by Osinka et al [96]. The sperm flagellum has an ultrastructurally comparable axonemal structure, but in addition the sperm tail contains accessory structures: the mitochondrial sheath (MS), fibrous sheath (FS) and outer dense fibres (ODFs) (Fig.…”