The MS4A family reveals a new mode of vertebrate olfaction

In mammals, odor perception is mediated by parallel sensory pathways that convey distinct information about the olfactory world. Multiple olfactory subsystems express characteristic seven-transmembrane G-protein coupled receptors in a one-receptor-per-neuron pattern that facilitates odor discrimination. However, the mechanisms underlying odor detection and sensory coding by one subsystem -- the olfactory "necklace" -- are unclear. Here, we report that the four-pass transmembrane MS4A proteins constitute a structurally novel family of olfactory receptors expressed within necklace sensory neurons. Individual necklace neurons co-express many MS4A proteins and are activated by multiple MS4A ligands; thus the necklace, which pools information from multiple receptors, appears organized more like known systems for taste than for smell. The MS4As therefore represent a novel mechanism for odor detection and define a distinct functional logic for mammalian olfaction.