Developing the polycystic kidney disease interactome
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disease causing numerous renal cysts to form leading to adult renal failure. The PKD-causing genes, polycystic kidney disease-1 and -2 (PKD1 and PKD2), encode for proteins polycystin-1 and -2 (PC1 and PC2). These proteins form a complex through their C-termini at cilia with mutations abolishing their interaction and impairing ciliary localization. We report the first use of proximity-dependent biotinylation for identification (BioID) to characterize the PC1 PC2 C-terminal complex binding partners in HEK 293 cells. We identify high- confidence interacting partners including an enrichment of cilia-related, transporter activity and trafficking genes. We report interesting PC1 interactions including Biogenesis of Lysosome-Related Organelles Complex-1 (BLOC-1) subunits and BLOC-One-Related Complex (BORC) subunits. We also report endoplasmic reticulum (ER)-related proteins that likely contribute to PC2 ER localization and function. Overall, this research hopes to contribute information to how PC1 and PC2 traffic and function at cilia.