Polycystin Ciliary Localization

The polycystins must ultimately be localized to cilia in order to carry out the sensory functions of the cell, whether it is a human renal epithelial cell or a worm sensory neuron. Remarkably little is known about how polycystins, signaling molecules, and structural components are targeted to the ciliary compartment and how this ciliary localization is maintained. We previously reported that dynamic phosphorylation on PKD-2/PC-2 is critical for its ciliary localization, and ubiquitylation, endocytosis, and sorting for lysosomal degradation may modulate the downregulation of the polycystins from cilia. Defects in this pathway result in accumulation of LOV-1/PKD-2 at the cilia base/(transition zone). We hypothesize that cilia base/(transition zone) is a critical site for ciliary proteins to be unloaded/loaded and recycled/degraded. More experimental approaches will be used to study the downregulation pathway and determine if the cilia base function as “hot spot” for shipping, receiving and downregulation.