ABSTRACT
While polycystin-1 (PC1) has long been regarded as being a subunit of a heteromeric polycystin-1/polycystin-2 (PC1-PC2) receptor-channel complex, its biochemical functions have remained elusive. Research going back to the 1990s has supported the concept that PC1 functions as an atypical G protein-coupled receptor (GPCR). This chapter reviews the methods and approaches taken to demonstrate that the C-terminal cytosolic tail (C-tail) of PC1 binds and activates heterotrimeric G proteins, which signal to downstream effectors. A 74–amino acid (aa) region of the membrane-proximal C-tail stably binds G-protein subunits, and this region contains a 20-aa peptide that stimulates G-protein nucleotide exchange. Mutagenesis and transient transfection studies have shown that the PC1 C-tail is able to mobilize intracellular Ca2+ and activate a number of signaling pathways including c-Jun N-terminal kinase (JNK), and the AP-1 and NFAT transcription factors in a Gα- and Gβγ-dependent fashion. The experimental methods discussed in this chapter have defined an essential function of PC1, which is to activate G proteins to initiate both downstream signal transduction and to regulate the PC1-PC2 channel.
