Polycystin Function

ADPKD (autosomal dominant polycystic kidney disease ), the most common genetic disease in human, affects 1 in 1000 individuals and is caused by defects in polycystin-1 (PC-1, encoded by PKD1) or polycystin-2 (PC-2, encoded by PKD2). Two evolutionarily conserved C. elegans polycystin homologues, called LOV-1 (for location of vulva 1) and PKD-2 (for polycystic kidney disease gene 2), are found to localize and function in the cilia of male-specific sensory neurons and may act in a sensory capacity to ¬regulate male sensory behaviors. Many basic questions in polycystin biology remain unresolved. First, is LOV-1/PC-1 cleaved in vivo and, if so, what is the significance of the cleavage? Second, do LOV-1/PC-1 and PKD-2/PC-2 interact to form a functional cation channel in a living animal? Third, what other signaling components are involved in the LOV-1/PKD-2 pathway? Finally, is there another sensory complex that functions with or in parallel to polycystins on cilia?