Light-induction of endocannabinoids and activation of <i>Drosophila</i> TRPC channels

<jats:title>Abstract</jats:title><jats:p><jats:italic>Drosophila</jats:italic> phototransduction represents a classical model for signaling cascades that culminate with activation of TRP channels. TRP and TRPL are the canonical TRP (TRPC) channels, which are gated by light stimulation of rhodopsin and engagement of Gq and phospholipase Cβ (PLC). Despite decades of investigation, the mechanism of TRP activation in photoreceptor cells is unresolved. Here, using a combination of genetics, lipidomics and Ca<jats:sup>2+</jats:sup> imaging, we found that light increased the levels of an abundant endocannabinoid, 2-linoleoyl glycerol (2-LG) <jats:italic>in vivo</jats:italic>. The elevation in 2-LG strictly depended on the PLC encoded by <jats:italic>norpA</jats:italic>. Moreover, this endocannabinoid upregulated TRPC-dependent Ca<jats:sup>2+</jats:sup> influx in a heterologous expression system and in dissociated ommatidia from compound eyes. We propose that 2-LG is a physiologically relevant endocannabinoid that activates TRPC channels in photoreceptor cells.</jats:p>