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

Abstract

Drosophila 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 q 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 2+ 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 norpA and inaE , respectively. This endocannabinoid facilitated TRPC-dependent Ca 2+ 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.

Functional relationship between peripheral thermosensation and behavioral thermoregulation

“…Lipid mediators derived from cell membrane lipids also directly activate TRP channels as was shown for mammalian TRPV activation by endocannabinoids such as 2-AG (2-arachidonoyl glycerol) and N-acylethanolamines ( Sisignano et al, 2014 ). In Drosophila , a recent study showed that 2-LG (2-linoleoyl glycerol), endocannabinoid derived from linoleic acid-containing phospholipids, activate TRP and TRPL, which is involved in visual signaling in the compound eye ( Sokabe et al, 2022 ).…”

TRP Channels in Cancer: Signaling Mechanisms and Translational Approaches

“…The main differences between the seven TRP channel subfamilies are found in the N-and C-terminal cytosolic domains, which contain putative protein inter-action and regulatory motifs [40]. TRP channels are activated in several ways: directly by endogenous agents, including diacylglycerols [41], phosphoinositides [42], eicosanoids [43], anandamide [44], and reactive oxygen species (ROS) and their byproducts [45,46], and by an unprecedented series of exogenous compounds, such as capsaicin [47], icilin [48], allicin [49], allyl isothiocyanate (AITC) [50,51], isopetasin [52], umbellulone [53,54], parthenolide [55], and acrolein [56], or indirectly, by intracellular mediators produced by the activation of G protein-coupled receptor (GPCR) or tyrosine kinases receptor [57].…”

Regulatory mechanisms controlling store-operated calcium entry

“…Isolated photoreceptor cells from drosophila wild type and rdgA (DAG kinase) mutants show constitutive TRP activity. Recently, endocannabinoids produced in Drosophila photoreceptor cells in response to light have been shown to activate TRP channels ( Sokabe et al, 2022 ). In addition, using flies engineered to express genetically encoded ER calcium indicator, the sodium/calcium exchanger has been shown to result in rapid calcium release from the ER upon light exposure ( Liu et al, 2020 ).…”