Ether phospholipids modulate somatosensory responses by tuning multiple receptor functions in Drosophila

PIEZO and TRP channels are receptors for physical stimuli such as mechanical touch and temperature in sensory neurons. As these receptors are localized in the plasma membrane, the modulation of their activities by membrane lipids has recently attracted attention. In this study, we focused on ether phospholipids (ePLs) enriched in neurons and analyzed their role in somatosensation using Drosophila. Reduced mechanosensory behavior was observed with ePL-synthesizing gene knockout or knockdown in PIEZO-expressing neurons. PIEZO activation was significantly augmented in the presence of ePLs. Furthermore, we observed that ePLs modulate the thermosensory behavior and reduce the temperature threshold of TRPA1. Finally, we revealed that ePLs affect membrane tension and lipid order of the plasma membrane in cultured cells. Our study identified ePLs as a modulator of a specific set of receptors for multiple somatosensory modalities, which underscores the significance of functional interaction between membrane lipids and sensory channel proteins.