An ammonium transporter is a non-canonical olfactory receptor for ammonia

Numerous hematophagous insects are attracted to ammonia, a volatile released in human sweat and breath.^1-3 Low levels of ammonia also attract non-biting insects such as the genetic model organism Drosophila melanogaster and several species of agricultural pests.^4,5 Two families of ligand-gated ion channels function as olfactory receptors in insects,^6-10 and studies have linked ammonia sensitivity to a particular olfactory receptor in Drosophila.^5,11,12 Given the widespread importance of ammonia to insect behavior, it is surprising that the genomes of most insects lack an ortholog of this gene.⁶ Here, we show that canonical olfactory receptors are not necessary for responses to ammonia in Drosophila. Instead, we demonstrate that a member of the ancient electrogenic ammonium transporter family, Amt, is likely a new type of olfactory receptor. We report two hitherto unidentified olfactory neuron populations that mediate neuronal and behavioral responses to ammonia in Drosophila. Their endogenous ammonia responses are lost in Amt mutant flies, and ectopic expression of either Drosophila or Anopheles Amt confers ammonia sensitivity. These results suggest that Amt is the first transporter known to function as an olfactory receptor in animals and that its function may be conserved across insect species.