| Caenorhabditis elegans male mating behavior provides a powerful model for studying the genetics of complex sensory behaviors. Male mating may be broken down into a series of stereotypical substeps: response, turning, vulva location, spicule insertion, and sperm transfer. Each step requires that the male senses stimuli from the hermaphrodite and integrates these sensory inputs into specific sensorimotor circuits. For my thesis, I dissected genetic, molecular and neural pathways underlying male mating behaviors in search of novel insights into fundamental biology of sensory behavior.; I mapped and cloned a mutant allele of the kinesin-like protein gene klp-6 that was originally isolated from a classical behavioral genetic screen. Male klp-6(sy511) mutants exhibit similar response and location of vulva (Lov) phenotypes like polycystin mutants lov-1 and pkd-2, which encode cilia sensory receptors orthologous to mammalian PC-1 and PC-2, respectively. klp-6 is expressed in all polycystin-expressing neurons and its protein product localizes to sensory cilia with polycystins. In klp-6( sy511) mutants, PKD-2 is mislocalized from its normal ciliary environment. Epistasis experiments reveal complex genetic interactions between klp-6, lov-1 and pkd-2 that I hypothesize arise from multiple sensory pathway interactions in a single neuron. The KLP-6 C-terminus dominantly effects mating behavior and PKD2 localization, indicating an auto-inhibitory function of the KLP-6 carboxy-tail. Combined, my data indicate that KLP-6 and the polycystins function in a common pathway, possibly as a motor-cargo unit. KLP-6 has single homologs in many vertebrate species, including human. I propose KLP-6 orthologs are evolutionarily conserved, transcriptionally selected units of polycystin function. Comparative analyses will provide significant insights into ADPKD, cilia, and the evolution of sensory behaviors.; Furthermore, I used reverse genetic approaches to dissect potential roles of the TRP superfamily of ion channels in male sensory behavior. Combining cellular, genetic, and molecular approaches, I demonstrated that the TRPV subfamily members OSM-9 and OCR-2 interact as an SPV-cilia sensory receptor required for sperm transfer behavior. Finally, I have generated a TRP proteome expression map that provides a valuable resource for studying cellular and molecular pathways of TRP superfamily members. |
