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Animals depend on their sense of smell to locate food, identify mates and evade danger. In mammals, olfactory perception typically relies on G protein–coupled receptor (GPCR) pathways. Insects, by contrast, use a distinct receptor system made up of odorant receptors (OrX) paired with a co-receptor known as Orco. For years, a key question has lingered: Do these insect receptors signal through GPCR-like routes or an entirely different mechanism?

To tackle this issue, a research team led by Prof. Kang Le from the Institute of Zoology of the Chinese Academy of Sciences (CAS), who is also a CAS member, has discovered that locusts bypass the classical GPCR pathway entirely. Instead, they rely on inositol 1,4,5-trisphosphate (IP₃)—a specific molecule—as the core second messenger in their olfactory signal transduction process.

Their , published in Science Advances on Sept. 10, map the complete pathway linking odor detection to behavioral responses in locusts.

To unravel this mechanism, the researchers used 4-vinylanisole (4VA) as a model. They discovered that the signal begins when two odorant-binding proteins, OBP10 and OBP13, capture the 4VA pheromone and deliver it to the olfactory receptor OR35 together with Orco co-receptor. Rather than activating GPCRs, the OR35–Orco receptor complex engages a lipid-binding protein, Clvs2, which facilitates the enrichment of PIP₂ lipids in cell membranes.

This step triggers the production of IP₃, which generates electrical signals in the antenna and is amplified in the brain's antennal lobe by the enzyme PLCe1. The cascade ultimately drives the locust's behavioral response.

Notably, the IP₃ pathway is not limited to pheromone sensing. Tests with plant volatiles, alarm pheromones, and sex pheromones revealed the same mechanism, suggesting that IP₃ serves as a universal second messenger in locust olfaction.

These findings establish a molecular chain: OBPs → OR35/Orco → Clvs2 → PLCe1 → IP₃. This discovery reshapes scientific understanding of how insects process chemical signals, the researchers noted. Additionally, the study provides a new conceptual basis for developing eco-friendly strategies to control locust populations.