A pheromone receptor mediates 11-cis-vaccenyl acetate-induced responses in Drosophila

Insect pheromones elicit stereotypic behaviors that are critical for survival and reproduction. Defining the relevant molecular mechanisms mediating pheromone signaling is an important step to manipulate pheromone-induced behaviors in pathogenic or agriculturally important pests. The only volatile pheromone identified in Drosophila is 11-cis-vaccenyl acetate (VA), a male-specific lipid that mediates aggregation behavior. VA activates a few dozen olfactory neurons located in T1 sensilla on the antenna of both male and female flies. Here, we identify a neuronal receptor required for VA sensitivity. We identified two mutants lacking functional T1 sensilla and show that the expression of the VA receptor is dramatically reduced or eliminated. Importantly, we show misexpression of this receptor in non-T1 neurons, normally insensitive to VA, confers pheromone sensitivity at physiologic concentrations. Sensitivity of T1 neurons to VA requires LUSH, an extracellular odorant-binding protein (OBP76a) present in the sensillum lymph bathing trichoid olfactory neuron dendrites. Here, we show LUSH are also required in non-T1 neurons misexpressing the receptor to respond to VA. These data provide new insight into the molecular components and neuronal basis of volatile pheromone perception.