Kidneys shaped

Polycystic kidney disease is characterized by the extensive formation of renal cysts, which can cause progressive renal failure. Most cases are due to autosomal dominant mutations of PKD1 — a gene that encodes polycystin-1 — but the mechanism underling this process remain unclear. In February 15 Journal of Clinical Investigation, Christian Nickel and colleagues from Yale University, USA, show that the polycystin-1 C-terminal fragment is responsible for triggering branching morphogenesis and migration of tubular kidney epithelial cells.

Nickel et al. used a retroviral gene transfer approach to express the cytoplasmic domain of polycystin-1 in murine inner medullary collecting duct cells (IMCDs). They found that overexpression of the C-terminal 112 amino acids of human polycystin-1 leads to greater cell motility, stimulates cell elongation and branching, and causes rounded clusters of IMCDs to generate tubules in culture (J Clin Invest 2002, 109:481-489).

"Our findings demonstrate that the C-terminal domain of polycystin-1, acting ...