The Cell Biology of the NIMA-Related Kinase Defective in Polycystic Kidney Disease

Polycystic kidney disease (PKD) affects one in 800 people worldwide and is the major reason for dialysis treatment and kidney transplantation. One of the most common genetic diseases in the world, PKD has many forms, ranging from aberrant cell proliferation in the kidney to defects in other organ systems, such as the liver and pancreas. This abnormal growth within kidneys and other organs eventually leads to organ failure. The age of onset and disease severity for PKD are highly variable and are affected by additional genetic mutations. Mouse models of the disease have been used to identify many of the genes involved in the polycystic pathology and to determine links between gene and disease. Many of these genes encode proteins that localize to the cilia, a hair-like cell projection that senses the extracellular environment of the cell. The loss of a cilium results in the inability of a cell to response to external cues controlling normal growth. It has been shown that the failure of a kidney cell to build cilia results in PKD. Nek8 is an enzyme which, when mutated, causes PKD in mice. Melissa Trapp’s work has shown that Nek8 is also found within the cilia. This research project is focused on the role of Nek8 within cells, particularly how mutated Nek8 can alter the cilium and cause defects in cell growth. By manipulating the protein levels in Nek8 within cultured kidney cells and introducing mutant forms of Nek8, she is examining the effects on ciliary assembly and cell proliferation. This research will contribute to the body of knowledge accumulating about Nek8 and the cause of PKD. It could also contribute to our understanding of other cystic kidney diseases.