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

Transient receptor potential (TRP) and PIEZO channels are known receptors for physical stimuli such as temperature and mechanical touch in sensory nerves. Since these receptors are localized in the plasma membrane, the regulation of sensory receptor activity by plasma membrane lipids has recently attracted attention. In this study, we focused on ether phospholipids (ePLs), which are abundant in neurons, and analyzed their role in somatosensation using Drosophila as a model. Reduced warmth avoidance was observed with ePL synthesizing gene knockout or knockdown in warmth-sensitive TRPA1-expressing neurons. The temperature threshold for Drosophila TRPA1 channels significantly decreased in presence of ePLs. In addition, we found that ePLs modulate the mechanosensory behavior and activation properties of the mechanosensitive channel PIEZO. Finally, we revealed that ePLs affect physicochemical properties of the plasma membrane, such as membrane tension and lipid order, in culture cells. Our study identified ePLs as crucial regulators of multiple somatosensation modalities in Drosophila . Effects due to alteration of cellular membrane properties and activity modulation of sensory receptors.