Conserved structural motifs in the central pair complex of eukaryotic flagella

Abstract

Cilia and flagella are conserved hair-like appendages of eukaryotic cells that function as sensing and motility generating organelles. Motility is driven by thousands of axonemal dyneins that require precise regulation. One essential motility regulator is the central pair complex (CPC) and many CPC defects cause paralysis of cilia/flagella. Several human diseases, such as immotile cilia syndrome, show CPC abnormalities, but little is known about the detailed three-dimensional structure and function of the CPC. The CPC is located in the center of typical [9+2] cilia/flagella and is composed of two singlet microtubules, each with a set of associated projections that extend toward the surrounding nine doublet microtubules. Using cryo-electron tomography coupled with subtomogram averaging, we visualized and compared the three-dimensional structures of the CPC in both the green alga Chlamydomonas and the sea urchin Strongylocentrotus at the highest resolution published to date. Despite the evolutionary distance between these species, their CPCs exhibit remarkable structural conservation. We identified several new projections, including those that form the elusive sheath, and show that the bridge has a more complex architecture than previously thought. Organism-specific differences include the presence of microtubule inner proteins in Chlamydomonas, but not Strongylocentrotus, and different overall outlines of the highly connected projection network, which forms a round-shaped cylinder in algae, but is more oval in sea urchin. These differences could be adaptations to the mechanical requirements of the rotating CPC in Chlamydomonas, compared to the Strongylocentrotus CPC which has a fixed orientation.

Mechanosignaling between central apparatus and radial spokes controls axonemal dynein activity

“…The difference in the 3D structures of C1a and C1b projections might explain their roles in CP-RS mechanosignaling (Fig. 6, D and E;Carbajal-González et al, 2013). The C1a projection looks like a fist extending from C1 (Fig.…”

Motility and more: the flagellum of Trypanosoma brucei

“…Adjacent doublets are connected via the nexin-dynein regulatory complex (NDRC) (Figure 2) 24, 25 . Radial spokes extend inward from each outer doublet and converge on the central pair apparatus, which includes the central pair microtubules and several, mostly unknown components that extend in a sheath-like structure around the central pair 26 .…”

A Structural Basis for How Motile Cilia Beat

“…Also illustrated are the locations and substructure of each inner dynein arm (I1/f dynein and dyneins a-g; Bui et al 2012, Heuser et al 2012b, Lin et al 2014, the N-DRC (Heuser et al 2009), the CSC (Dymek et al 2011, Heuser et al 2012a, and the radial spokes (Pigino et al 2011, Barber et al 2012, Oda et al 2014). In addition, cryo-ET has revealed the substructure of the central pair apparatus (Carbajal-Gonzalez et al 2013, Oda et al 2014). …”