UCSF

This dissertation explores how members of the largest class of signaling receptors, seven-transmembrane receptors (7TMRs), are targeted to the primary cilium, a protrusion of the plasma membrane that acts as a cellular signaling antennae. The study primarily focuses on how the D1 dopamine receptor (D1R) is targeted to the cilium with the assumption that other cilia-localized 7TMRs likely use the same mechanism. The introduction gives an overview of how primary cilia function as an important location for receptor signaling, provides basic information on cilia formation and function, reviews models for trafficking pathways to the cilium, and details what is currently known about receptor ciliary targeting sequences and which proteins function in ciliary receptor delivery. Chapter 2 contains my findings on D1R dynamics within the cilium, the membrane source of ciliary D1Rs, and the D1R ciliary targeting determinant. In addition, the 2nd chapter identifies roles for several proteins, IFT-B, KIF17, and Rab23, in mediating D1R ciliary localization. The included work uses a combination of fixed-cell imaging, live-cell imaging, biochemistry, genetic manipulations, and flow cytometry analysis. Chapter 3 delves deeper into the analysis of the results from chapter 2, explains how these findings contribute to and advance the receptor ciliary localization field, and proposes future directions to continue this research.