G Protein‐Coupled Receptor Signal Intersection at the Primary Cilium

ABSTRACT Primary cilia are singular projections that extend from the surface of most vertebrate cell types. The surface area of the primary cilium (PC) is estimated to represent only 1/100 th of the total membrane surface of an average cell. Despite this, the PC provides essential contributions to inter‐ and intracellular communication by housing receptors and downstream effectors for myriad cell‐signaling cascades. G protein‐coupled receptors (GPCRs) commonly enrich along ciliary membranes to control a diverse range of cellular behaviors by signaling through a shared pool of downstream effectors. This suggests the hypothesis that the PC provides an environment that is conducive to complementary or competitive GPCR Signal Crosstalk. In this Hypothesis Bio Essay, we use the Sonic Hedgehog (SHH) pathway as a case study to inform models of how GPCR signals could intersect in primary cilia and suggest general strategies to test each model.