The transition zone: an essential functional compartment of cilia

Abstract

Recent studies of the primary cilium have begun to provide further insights into ciliary ultrastructure, with an emerging picture of complex compartmentalization and molecular components that combine in functional modules. Many proteins that are mutated in ciliopathies are localized to the transition zone, a compartment of the proximal region of the cilium. The loss of these components can disrupt ciliary functions such as the control of protein entry and exit from the cilium, the possible trafficking of essential ciliary components, and the regulation of signaling cascades and control of the cell cycle. The discovery of functional modules within the primary cilium may help in understanding the variable phenotypes and pleiotropy in ciliopathies.

Figure 1

This figure shows schematic representation of cilia ultrastructure with cross-sections at the level of the basal body, transition fibers, transition zone and axoneme in motile and non-motile cilia. On the left hand side, is an enlarged immunofluorescence micrograph of a single primary cilium on an IMCD3 epithelial cell immunostained for the cilia marker acetylated α-tubulin (blue), the basal body marker γ-tubulin (red), and transmembrane protein (TMEM) 216 (green) which localizes to the transition zone. Scale bar = 1 μm.

Figure 2

Localization of the indicated proteins (coloured ovals) to sub-ciliary compartments (pale blue, axoneme; grey, inversin compartment; pink, transition zone; dark blue, basal body; grey with dashed square , centriolar satellites) are represented based on biochemical and genetic interaction data from four recent studies of the composition of the transition zone (Sang et al. 2011,Garcia-Gonzalo et al. 2011,Williams et al. 2011 and Huang et al. 2011; each indicated at the top of each section). White text indicates common components identified by different studies; dark lines indicate an interaction identified by MS/MS; a dashed line indicates a genetic interaction; overlapping ellipses indicated a direct interaction. The model system(s) used to generate these data are also indicated for each study.

Figure 3

Five ciliopathies with extensive genetic heterogeneity and pleiotropy (BBS, Bardet-Biedl syndrome; JBTS, Joubert syndrome; MKS, Meckel-Gruber syndrome; NPHP, nephronophthisis; SLS, Senior-Løken syndrome) are indicated by ovals of different colour, with the ciliary proteins mutated as a known cause of each disorder indicated by the coloured lines.