Ciliary Tip Signaling Compartment Is Formed and Maintained by Intraflagellar Transport
Current Biology , Volume 30 - Issue 21 p. 4299- +
Primary cilia are ubiquitous antenna-like organelles that mediate cellular signaling and represent hotspots for human diseases termed ciliopathies. Within cilia, subcompartments are established to support signal transduction pathways, including Hedgehog signaling. How these compartments are formed and maintained remains largely unknown. Cilia use two mechanisms, a trafficking system and a diffusion barrier, to regulate the trafficking of proteins into, within, and out of cilia. The main ciliary trafficking machinery, intraflagellar transport (IFT), facilitates bidirectional transport of cargo, including signaling proteins, from the base (basal body) to the tip of the axoneme . Anterograde IFT to the tip relies on kinesins, and cytoplasmic dynein enables retrograde transport back [2, 3]. To help confine proteins to cilia, a subdomain immediately distal to the basal body, called the transition zone (TZ), acts as a diffusion barrier for both membrane and soluble proteins [4–6]. Here, we show that in Caenorhabditis elegans a salt-sensing receptor-type guanylate cyclase, GCY-22, accumulates at a high concentration within a subcompartment at the distal region of the cilium. Targeting of GCY-22 to the ciliary tip is dynamic, requiring the IFT system. Disruption of the TZ barrier or IFT trafficking causes GCY-22 protein mislocalization and defects in the formation and maintenance of the ciliary tip compartment. Structure-function studies uncovered GCY-22 protein domains needed for entry and tip localization. Together, our findings provide mechanistic insights into the formation and maintenance of a novel subdomain at the cilium tip that contributes to the behavioral response to NaCl.
|Organisation||Department of Pathology|
van der Burght, S.N., Rademakers, S, Johnson, JL, Li, CM, Kremers, G.J, Houtsmuller, A.B, … Jansen, A.J.G. (2020). Ciliary Tip Signaling Compartment Is Formed and Maintained by Intraflagellar Transport. Current Biology, 30(21), 4299–429+. doi:10.1016/j.cub.2020.08.032