The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway

Autosomal dominant polycystic kidney disease (ADPKD) strikes 1 in 1000 indi viduals and often results in end-stage renal failure. Mutations in either P KD1 or PKD2 account for 95% of all cases [1 -3]. It has recently been demon strated that polycystin-1 and polycystin-2 (encoded by PKD1 and PKD2, respe ctively) 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 resul t in identical male sensory behavioral defects. Also, pkd-2;lov-1 double mu tants 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 t he same male-specific sensory neurons and are concentrated in cilia and cel l bodies. Cytoplasmic, nonnuclear staining in cell bodies is punctate, sugg esting 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. elegan s autosomal recessive PKD gene osm-5 [6-8], the cilia of lov-1 and pkd-2 si ngle mutants and of lov-1;pkd-2 double mutants are normal as judged by elec tron microscopy, demonstrating that lov-1 and pkd-2 are not required for ul trastructural development of male-specific sensory cilia.