A lipid required for vision and identified in fruit flies

Decades of studies of Drosophila vision have uncovered several components required for the signaling events upon light stimulation. Light first switches on the light-sensitive rhodopsin and, after several intermediate steps, leads to the activation of transient receptor potential (TRP) channels. It is believed that lipids lead to the opening of TRP channels and the stimulation of photoreceptor cells. However, the essential lipid molecules that directly activate TRP channels have been unclear. In this study, researchers identified an endocannabinoid that plays an important role in channel activation in photoreceptor cells.

Drosophila visual transduction is a classic model of signaling cascades culminating in the activation of TRP cation channels. In humans, these channels play many roles, including pain sensation, taste, and light detection. In Drosophila, light stimulates rhodopsin in photoreceptor cells, thereby facilitating activation of a protein called Gq. The Gq then activates an enzyme, phospholipase C (PLC), to produce a lipid – diacylglycerol (DAG). The TRP channels require DAG or a subsequently produced lipid, although the exact lipid was not known.

Takaaki Sokabe of the National Institute for Physiological Sciences and Craig Montell of the University of California, Santa Barbara found a lipid – an endocannabinoid – that increased upon light stimulation and activated the TRP and TRPL channels. The particular endocannabinoid that activates these channels, 2-linoleoylglycerol (2-LG), is related to the active ingredient in marijuana, tetrahydrocannabinol (THC). They recently published their results in Scientific signaling.

“We expected that we could find the essential lipids for the activation of the TRP channels by identifying lipids that increased upon light stimulation in fly heads,” says Sokabe. “It wasn’t that easy, though. We first spent five years creating conditions to stably observe changes in lipids with hundreds of flies in each sample.”

These efforts led to the demonstration that 2-LG increased when illuminated. This change in 2-LG levels was dependent on PLC and another enzyme called DAG lipase, which has been reported to be involved in visual transduction. In addition, they showed that 2-LG stimulated the TRP channels in isolated photoreceptor cells.

“Identifying the endocannabinoid in the cascade at least partially bridges the gap between DAG production and TRP channel activation,” says Takaaki Sokabe. “The same signaling cascade is conserved in one type of mammalian photoreceptor cell, and the mechanism may be applicable to other TRP channel-dependent cascades in different cell types.”

This work could advance our understanding of visual systems and other sensory systems.