title: The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) strikes 1 in 1000 individuals and often results in end-stage renal failure. Mutations in either PKD1 or PKD2 account for 95% of all cases [1-3]. It has recently been demonstrated that polycystin-1 and polycystin-2 (encoded by PKD1 and PKD2, respectively) assemble to form a cation channel in vitro [4]. Here we determine that the Caenorhabditis elegans PKD1 and PKD2 homologs, lov-1 [5] and pkd-2, act in the same pathway in vivo. Mutations in either lov-1 or pkd-2 result in identical male sensory behavioral defects. Also, pkd-2;lov-1 double mutants are no more severe than either of the single mutants, indicating that lov-1 and pkd-2 act together. LOV-1::GFP and PKD-2::GFP are expressed in the same male-specific sensory neurons and are concentrated in cilia and cell bodies. Cytoplasmic, nonnuclear staining in cell bodies is punctate, suggesting that one pool of PKD-2 is localized to intracellular membranes while another is found in sensory cilia. In contrast to defects in the C. elegans autosomal recessive PKD gene osm-5 [6-8], the cilia of lov-1 and pkd-2 single mutants and of lov-1;pkd-2 double mutants are normal as judged by electron microscopy, demonstrating that lov-1 and pkd-2 are not required for ultrastructural development of male-specific sensory cilia.
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA. mmbarr@pharmacy.wisc.edu
authors.forename: M M
authors.initials: MM
authors.lastname: Barr
authors.forename: J
authors.initials: J
authors.lastname: DeModena
authors.forename: D
authors.initials: D
authors.lastname: Braun
authors.forename: C Q
authors.initials: CQ
authors.lastname: Nguyen
authors.forename: D H
authors.initials: DH
authors.lastname: Hall
authors.forename: P W
authors.initials: PW
authors.lastname: Sternberg
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016891:Polycystic Kidney, Autosomal Dominant; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D050396:TRPP Cation Channels
chemical_list: D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D050396:TRPP Cation Channels