Functional characterization of the C. elegans nephrocystins NPHP-1 and NPHP-4 and their role in cilia and male sensory behaviors

Exp Cell Res. 2005 May 1;305(2):333-42. doi: 10.1016/j.yexcr.2005.01.008.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / analysis
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Cilia / chemistry
  • Cilia / physiology*
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / genetics
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / metabolism
  • Neurons, Afferent / chemistry
  • Neurons, Afferent / metabolism*
  • Sequence Deletion / genetics
  • Signal Transduction
  • TRPP Cation Channels

Substances

  • Caenorhabditis elegans Proteins
  • Membrane Proteins
  • TRPP Cation Channels
  • enhanced green fluorescent protein
  • nephrocystin 1, C elegans
  • nephrocystin 4, C elegans
  • polycystic kidney disease 2 protein
  • Green Fluorescent Proteins