Autosomal dominant (AD) polycystic kidney disease (PKD) is the most common genetic cause of end-stage renal failure. ADPKD is primarily characterized by the development and enlargement of hundreds of fluid-filled cysts that arise from epithelia-lined tubules within both kidneys. Cystic epithelial cells exhibit abnormal phenotypes that include increased proliferation, transepithelial fluid secretion, extracellular matrix deposition and apoptosis.

ADPKD is a systemic disease associated with cysts in the liver, cerebral aneurysms, hypertension, cardiac valve abnormalites, left ventricle hypertrophy and endothelial dysfunction. 

Mutations within the PKD1 gene, encoding polycystin-1 (PC1) protein, account for 85% of ADPKD cases, while the remainder are due to mutations within the PKD2 gene encoding polycystin-2 (PC2). Although ADPKD is inherited in a dominant fashion, cyst initiation is thought to require the functional level of either PC1 or PC2 protein to drop below a critical threshold.

PC1 is a large, 11-transmembrane domain receptor that activates multiple signaling pathways, including the binding and activation of heterotrimeric G-proteins. PC-2 is a 6-transmembrane, non-selective cation channel.

Together, PC1 and PC2 are believed to form a membrane receptor/ion channel signaling complex and are found at multiple cellular locations, including the primary cilium. Within the primary cilium, the PC1-PC2 complex are thought to mediate fluid shear stress-induced intracellular calcium signaling that is required for maintaining renal cell differentiation and tubular structure.

Robin L. Maser, Ph.D.
Associate Professor
Lab Director