Quality Control of the cilia proteome

PROJECT SUMMARY Primary cilia organize signaling pathways such as vision, olfaction and Hedgehog signaling and dysfunction of cilia causes a host of symptoms in disease collectively known as ciliopathies. The movements of signaling receptors into, inside and out of cilium are critical for the correct regulation of these pathways. Past work from the lab identified two paths for the regulated exit of signaling receptors out of cilia. One route goes back into the cell and has now been extensively characterized. Another route packages signaling receptors into extracellular vesicles (EVs) and its mechanisms remain poorly understood. The major goal of this proposal is to determine the molecular mechanisms for signaling receptor packaging into ciliary EVs. A major goal of this proposal is the generate genetically encoded disrupters of ciliary EV shedding. These tools will enable a rigorously test of the physiological importance of ectocytosis.