A latent capacity of the C. elegans polycystins 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.
Center for Neural Development and Disease, University of Rochester, Rochester, NY 14642, USA.
Renee M
RM
Miller
Douglas S
DS
Portman
D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D021381:Protein Transport; D011984:Sensory Receptor Cells / Q000378:metabolism*; D012727:Sex Characteristics; D015398:Signal Transduction; D050396:TRPP Cation Channels / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D050396:TRPP Cation Channels