Endocannabinoids produced in photoreceptor cells in response to light activate TRP channels

TitleEndocannabinoids produced in photoreceptor cells in response to light activate TRP channels
Publication TypeJournal Article
Year of Publication2022
AuthorsSokabe T, Bradshaw HB, Tominaga M, Leishman E, Chandel A, Montell C
JournalSci Signal
Volume15
Issue755
Paginationeabl6179
Date Published2022 Oct 11
ISSN1937-9145
Abstract

phototransduction is a model for signaling cascades that culminate in the activation of transient receptor potential (TRP) cation channels. TRP and TRPL are the canonical TRP (TRPC) channels that are regulated by light stimulation of rhodopsin and engagement of Gα and phospholipase Cβ (PLC). Lipid metabolite(s) generated downstream of PLC are essential for the activation of the TRPC channels in photoreceptor cells. We sought to identify the key lipids produced subsequent to PLC stimulation that contribute to channel activation. Here, using genetics, lipid analysis, and Ca imaging, we found that light increased the amount of an abundant endocannabinoid, 2-linoleoyl glycerol (2-LG), in vivo. The increase in 2-LG amounts depended on the PLC and diacylglycerol lipase encoded by and , respectively. This endocannabinoid facilitated TRPC-dependent Ca influx in a heterologous expression system and in dissociated ommatidia from compound eyes. Moreover, 2-LG and mechanical stimulation cooperatively activated TRPC channels in ommatidia. We propose that 2-LG is a physiologically relevant endocannabinoid that activates TRPC channels in photoreceptor cells.

DOI10.1126/scisignal.abl6179
Alternate JournalSci Signal
PubMed ID36219683