Species-specific chemical communication mediated by mixtures of released chemicals called pheromones regulates a broad range of social behaviors. Similar to other animal pheromones, C. elegans pheromone elicits both long-term ''primer'' effects on development by regulating entry into the alternate dauer developmental stage, as well as immediate ''releaser'' effects on adult sexual behavior (Golden and Riddle, 1982; Srinivasan et al., 2008). Dauer pheromone is a complex mixture of structurally related derivatives of the dideoxy sugar ascarylose (Jeong et al., 2005; Butcher et al., 2007, 2008). The signaling pathways required for dauer pheromone responses are unknown. We identified two G protein-coupled receptors,
srbc-64 and
srbc-66, that mediate the dauer regulatory effects of dauer pheromone.
srbc-64 and/or -66 null mutants exhibit strong defects in dauer formation and fail to downregulate
daf-7 TGF-b and
str-3 chemoreceptor gene expression in the ASI chemosensory neurons in response to a subset of dauer pheromone components. However, adult responses to pheromone are unaffected. Both
srbc-64 and -66 chemoreceptors are expressed exclusively in the ASK chemosensory neurons, and full-length GFP-tagged SRBC-64 and -66 proteins are localized to the sensory cilia. Animals lacking the ASK neurons exhibit strong defects in dauer formation, suggesting that the ASK neurons are the major sensory neuron type regulating pheromone-mediated dauer formation. Heterologous expression of both, but not each receptor alone, in the HEK293 cells are sufficient to confer pheromone-mediated responses, further indicating that SRBC-64 and -66 are receptors for dauer pheromone components in the dauer formation pathway. These chemoreceptors are members of a Caenorhabditis-specific subfamily that has undergone extensive expansion in C. elegans (Thomas and Robertson, 2008). We propose that expansion of the SRBC subfamily may contribute to the fidelity and diversity of the pheromone response in C. elegans. Current experiments are aimed at identifying the neurons and receptors that mediate dauer formation in response to additional pheromone components, and the signaling pathways that transmit pheromone information from the ASK to the ASI neurons to regulate dauer formation (see abstract by Zeiger et al).