Cilia are located at the distal ends of dendrites of C. elegans sensory neurons, where they perceive a variety of environmental cues and modulate worm behavior. Specialization of cilia is achieved by targeting distinct sensory receptors and signaling molecules to the cilia where they perform their sensory functions. How sensory receptors localize to cilia in C. elegans sensory neurons is largely unknown.
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic disorders in human (Igarashi and Somlo, 2002). Mutations in either PKD1 or PKD2 account for ~95% of ADPKD cases (Hughes et al., 1995; Mochizuki et al., 1996). Polycystin-1 (PC-1) and polycystin-2 (PC-2), encoded by PKD1 and PKD2 respectively, localize to cilia in kidney epithelia where they function in a mechanosensory capacity (Pazour et al., 2002; Yoder et al., 2002;Nauli et al., 2003). LOV-1 and PKD-2, the C. elegans homologues of PC-1 and PC-2 respectively, regulate male mating behaviors and localize to cilia of male specific sensory neurons (Barr et al., 2001; Barr and Sternberg, 1999). Identifying the mechanisms responsible for targeting PKD-2 to cilia may provide important insights into human ciliary diseases.
To identify genes regulating ciliary targeting of PKD-2, we screened for mutations that disrupt the localization of GFP-tagged PKD-2 (PKD-2::GFP). Cil (ciliary localization) mutants are categorized into three phenotypic groups. Class I Cil mutants display an accumulation of PKD-2::GFP in ciliary membrane and ciliary base (transition zone). Class I genes may potentially modulate PKD-2 receptor downregulation or ciliogenesis. In Class II Cil mutants, PKD-2::GFP is inappropriately distributed throughout the neurons including dendrites and axons. These genes may function to target PKD-2 specifically to dendrites or cilia. Lastly, mutations in Class III genes affect the level or pattern of PKD-2:GFP expression, suggesting these genes may regulate
pkd-2 transcription. Cil mutants exhibit male mating behavior defects, supporting our hypothesis that mislocalization of PKD-2 sensory receptor results in sensation defects. We will present Cil mutant mapping data and phenotypic characterization, including analysis of sensory behaviors, ciliogenesis, PKD-2::GFP dendritic motility, and localization of other ciliary receptors.