A latent capacity of theC. eleganspolycystins to disrupt sensory transduction is repressed by the single-pass ciliary membrane protein CWP-5

Autosomal dominant polycystic kidney disease (ADPKD) results from loss-of-function mutations in PKD1 or PKD2. The products of these genes, the polycystins PC-1 and PC-2, form a transmembrane channel that is necessary for flow sensing by renal cilia. In C. elegans, the polycystin orthologs LOV-1 and PKD-2 function in sensory neurons that mediate male mating behavior. Here, we report that the novel single-pass membrane protein CWP-5 is necessary for polycystin signaling during the response step of mating behavior. As with the polycystins, CWP-5 localizes to neuronal cilia; this localization requires LOV-1. The response defect of cwp-5 mutants does not appear to result from disruption of ciliogenesis or polycystin localization. Instead, genetic and behavioral analyses indicate that CWP-5 represses a previously undescribed antagonistic effect of the polycystins on sensory function. Although cwp-5 does not have a primary-sequence ortholog in vertebrates, it has intriguing parallels with the autosomal recessive PKD gene FPC (also known as PKHD1). Together, this study identifies a new component of C. elegans polycystin signaling, demonstrates that the polycystins have a latent capacity to hinder sensory transduction, and suggests that aberrant functions of the polycystins could contribute to the pathogenesis of PKD.