Abstract
Coordinated behavior in response to environmental stimuli is a fundamental biological process in eukaryotes. The nematode Caenorhabditis elegans is an excellent model organism for investigating the mechanism underlying transduction of environmental stimuli, partly due to its 302 stereotypically-connected neurons. Sixty of these neurons feature primary cilia – highly conserved sensory organelles necessary for an immense repertoire of behaviors such as dauer diapause entry in response to cilia-dependent inputs including pheromones. Ser/Thr kinase encoding gene F32B6.10 was identified in a screen for novel regulators of pheromone responses in C. elegans, and disruption of its function manifests in dauer formation defects. An F32B6.10 ortholog in mammals, Tau tubulin kinase 2 (ttbk-2) has been shown to regulate initiation of ciliogenesis by promoting the recruitment of proteins necessary for cilia assembly. I hypothesized that F32B6.10 and other ttbk-2 homologs function in sensory signal transduction by regulating C. elegans ciliogenesis. I confirmed three putative ttbks (F32B6.10, W01B6.2, and C04G2.2) contribute to pheromone-induced dauer formation, but found no evidence suggesting that the putative ttbks function in ciliogenesis based on wildtype lipophilic dye-uptake and cilia morphology in neurons natively expressing these molecules. While rescue experiments show that these genes mainly function in the sensory neurons ASK and ASI, sub-cellular localization data suggest these molecules do not localize to the cilia. My previous work demonstrated ciliary GPCR localization relies on cell- and receptor-specific trans-acting mechanisms and I therefore hypothesize that these putative TTBKs function as trans-acting factors in pheromone receptor localization. Future experiments will address whether localization of known pheromone receptors is affected in ttbk mutants. These experiments will provide insight into the contribution of these highly conserved proteins in C. elegans sensory transduction.