New lipid involved essential for maintaining normal pain and heat sensations discovered by NIPS

A research group led by Associate Professor Takaaki Sokabe and Assistant Professor Takuto Suito (at the time of the research) of the Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences (NIPS), in collaboration with Nagoya University, the University of Shizuoka, and Nagoya City University, has discovered a new lipid called "Ether Phospholipid (ePL)" that is essential for maintaining normal pain and temperature sensations in living organisms. They confirmed that when Drosophila (fruit flies) lose this lipid, their escape behavior from contact and thermal stimuli weakens. ePL and its synthetic enzymes also exist in humans. These findings are expected to lead to the development of methods for maintaining sensory functions and improving sensory disorders. The results were published in the journal iScience on March 18.

Animals are able to escape danger when PIEZO channels, which act as sensors for contact stimuli, and TRP channels, which act as temperature sensors, function normally. These sensor molecules were the subject of the 2021 Nobel Prize. However, many aspects of how these functions are maintained remain unknown.

In this study, the research group focused on lipids. Since sensory sensors for contact and temperature are abundant in sensory nerves and the brain, it was considered highly likely that the lipids involved in these sensory functions would also be widely distributed in those areas. Therefore, they conducted experiments using Drosophila larvae. By visualizing "AGPS," an enzyme indispensable for the synthesis of ePL, one of the lipids in the cell membrane, they discovered that this enzyme is highly prevalent in sensory nerves and the brain. The response to contact and temperature stimuli was then examined in Drosophila larvae without ePL.

As a result, they found that larvae without ePL showed a weakened escape response when poked with a needle and were less effective at avoiding hot temperatures that were unsuitable for survival. Furthermore, they investigated how ePL relates to the functions of the PIEZO channel (contact stimulus sensor) and the TRPA1 channel (temperature sensor).

The group found that when ePL is absent from the cell membrane, the responses of these sensory sensor molecules become sluggish. These findings indicate that ePL regulates the function of multiple sensor molecules through changes in the properties of the cell membranes of sensory nerves.

Sokabe said, "It is a new discovery that a lipid that was previously known to be abundant in the brains of humans and other animals is responsible for the regulation of sensory functions. Since it is known that this lipid decreases with age, we intend to investigate its relationship with aging and sensory dysfunction in the future."

Journal Information
Publication: iScience
Title: Ether phospholipids modulate somatosensory responses by tuning multiple receptor functions in Drosophila
DOI: 10.1016/j.isci.2026.115209