title: Functional characterization of the C. elegans nephrocystins NPHP-1 and NPHP-4 and their role in cilia and male sensory behaviors.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) and nephronophthisis (NPH) share two common features: cystic kidneys and ciliary localized gene products. Mutation in either the PKD1 or PKD2 gene accounts for 95% of all ADPKD cases. Mutation in one of four genes (NPHP1-4) results in nephronophthisis. The NPHP1, NPHP2, PKD1, and PKD2 protein products (nephrocystin-1, nephrocystin-2 or inversin, polycystin-1, and polycystin-2, respectively) localize to primary cilia of renal epithelia. However, the relationship between the nephrocystins and polycystins, if any, is unknown. In the nematode Caenorhabditis elegans, the LOV-1 and PKD-2 polycystins localize to male-specific sensory cilia and are required for male mating behaviors. To test the hypothesis that ADPKD and NPH cysts arise from a common defect in cilia, we characterized the C. elegans homologs of NPHP1 and NPHP4. C. elegans nphp-1 and nphp-4 are expressed in a subset of sensory neurons. GFP-tagged NPHP-1 and NPHP-4 proteins localize to ciliated sensory endings of dendrites and colocalize with PKD-2 in male-specific sensory cilia. The cilia of nphp-1(ok500) and nphp-4(tm925) mutants are intact. nphp-1; nphp-4 double, but not single, mutant males are response defective. We propose that NPHP-1 and NPHP-4 proteins play important and redundant roles in facilitating ciliary sensory signal transduction.
authors.affiliation: Laboratory of Genetics, University of Wisconsin, School of Pharmacy, 777 Highland Avenue, Madison, WI 53705, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Jauregui
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Barr
mesh_terms: D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002923:Cilia / Q000737:chemistry / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D009475:Neurons, Afferent / Q000737:chemistry / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D015398:Signal Transduction; D050396:TRPP Cation Channels
chemical_list: D029742:Caenorhabditis elegans Proteins; D049452:Green Fluorescent Proteins; D008565:Membrane Proteins; D050396:TRPP Cation Channels; C485184:enhanced green fluorescent protein; C501204:nephrocystin 1, C elegans; C501205:nephrocystin 4, C elegans