Polycystic Kidney Disease and Protein Localization : Analysis of the Role of gar-3 in Protein Localization to Cilia in Caenorhabditis Elegans

Abstract

Gar-3, a gene that encodes a G protein-coupled acetylcholine receptor, has been shown to play roles in both neurotransmission and protein localization to synapses. We asked whether gar-3 also affects the localization of PKD-2 protein to primary cilia in C. elegans, a free-living nematode. Dysregulated PKD-2 localization has been linked to polycystic kidney disease. Thus, understanding the factors that mediate PKD-2 protein localization to cilia might help us better understand the molecular basis of polycystic kidney disease. We chose to utilize C. elegans as our model organism because it is transparent and has a cilia structure similar to cilia found in mammalian kidneys. In order to address our question, we used both genetic and reverse genetic techniques to reduce gar-3 gene expression in C. elegans transgenic for PKD2::GFP. This allowed us to use fluorescent microscopy to assess PKD-2 localization to primary cilia in a living animal and draw conclusions about how this might affect the progression of polycystic kidney disease. If gar-3 is associated with PKD-2 localization, this would provide new insight into polycystic kidney disease.