Ether phospholipids modulate somatosensory responses by tuning multiple receptor functions inDrosophila

Abstract

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 usingDrosophilaas a model. Reduced warmth avoidance was observed with ePL synthesizing gene knockout or knockdown in warmth-sensitive TRPA1-expressing neurons. The temperature threshold forDrosophilaTRPA1 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 inDrosophila. Effects due to alteration of cellular membrane properties and activity modulation of sensory receptors.

Functional relationship between peripheral thermosensation and behavioral thermoregulation

“…Recently, an effect of ether phospholipids on TRPA1 channel activity was demonstrated. Drosophila lacking the gene encoding AGPS, an enzyme involved in ether lipid synthesis, exhibit abnormalities in sensation of hot temperatures that results in an increase in preferred temperature ( Suito et al, 2023 ). Suppressing AGPS expression in TRPA1-expressing neurons also produces similar phenotypic patterns.…”

“…Electrophysiological analysis using TRPA1 expressed in Drosophila cell lines showed that ether lipids can alter the activation temperature threshold of TRPA1 channels. Ether lipids alter membrane tension and lipid order phase of cell membranes ( Suito et al, 2023 ). Thus, the physicochemical properties of cellular membranes may determine sensory properties.…”