Signaling in the primary cilium through the lens of the Hedgehog pathway

Cilia are microtubule-based, cell-surface projections whose machinery is evolutionarily conserved. In vertebrates, cilia are observed on almost every cell type and are either motile or immotile. Immotile sensory, or primary cilia, are responsive to extracellular ligands and signals. Cilia can be thought of as compartments, functionally distinct from the cell that provides an environment for signaling cascades. Hedgehog is a critical developmental signaling pathway which is functionally linked to primary cilia in vertebrates. The major components of the vertebrate Hedgehog signaling pathway dynamically localize to the ciliary compartment and ciliary membrane. Critically, G-protein coupled receptor (GPCR) Smoothened, the obligate transducer of the pathway, is enriched and activated in the cilium. While Smoothened is the most intensely studied ciliary receptor, many GPCRs localize within cilia. Understanding the link between Smoothened and cilia defines common features, and distinctions, of GPCR signaling within the primary cilium. This article is categorized under: Signaling Pathways > Global Signaling Mechanisms Signaling Pathways > Cell Fate Signaling.