Animals rely on smell to find food, recognize mates, and avoid danger. In mammals, olfactory perception typically depends on G protein–coupled receptor (GPCR) pathways. Insects, however, employ a different receptor system composed of odorant receptors (OrX) paired with a co-receptor (Orco). Whether these receptors signal through GPCR-like routes or a distinct mechanism has long remained unresolved.

A new study published in Science Advances provides the answer. The team led by Academician KANG Le at the Institute of Zoology, Chinese Academy of Sciences, reports that locusts bypass the classical GPCR pathway. Instead, they rely on inositol 1,4,5-trisphosphate (IP₃) as the core second messenger in olfactory signal transduction. The paper,“Locusts adopt IP₃ as a second mssenger for olfactory signal transduction”, maps a complete pathway from odor detection to behavioral response.

Using the locust aggregation pheromone 4-vinylanisole (4VA) as a model, the researchers discovered that the signal begins when two odorant-binding proteins, OBP10 and OBP13, capture the pheromone and deliver it to the olfactory receptor OR35 together with Orco. Rather than activating GPCRs, the 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.

Importantly, 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.

The findings establish the molecular chain OBPs–OR35/Orco–Clvs2–PLCe1–IP₃, reshaping our understanding of how insects process chemical signals. By proving that IP₃ can function independently of GPCRs, the study not only revises long-held views of second messenger signaling, but also broadens the theoretical framework of sensory neuroscience and insect chemical ecology. At the same time, it provides a new conceptual basis for developing eco-friendly pest management strategies. Instead of relying on broad-spectrum pesticides, future approaches may precisely interfere with pheromone perception to regulate insect behavior. This work therefore represents both a fundamental scientific advance and a potential technological leap, with implications for food security, biodiversity conservation, and sustainable agriculture.

Figure: A complete olfactory transduction pathway in locusts.（Image by Prof. KANG Le’s Lab）