Abstract
The TRP family of ion channels mediates a wide range of calcium-influx phenomena in eukaryotic cells. Many members of this family are activated downstream of phosphoinositide hydrolysis but the subsequent steps that lead to TRP channel activation in vivo remain unclear. Recently, the lipid products of phosphoinositide hydrolysis (such as diacylglycerol and its metabolites) have been implicated in activating TRP channels in both Drosophila and mammals. In Drosophila photoreceptors, lack of diacylglycerol kinase (DGK) activity (encoded by rdgA) leads to both constitutive TRP-channel activity and retinal degeneration. In this study, using a novel forward-genetic screen, we identified InaD, a multivalent PDZ domain protein as a suppresser of retinal degeneration in rdgA mutants. We show that InaD suppresses rdgA and that the rescue is correlated with reduced levels of phospholipase Cbeta (PLCbeta), a key enzyme for TRP channel activation. Furthermore, we show that light, Gq and PLCbeta all modulate retinal degeneration in rdgA. The results demonstrate a previously unknown requirement for a balance of PLCbeta and DGK activity for retinal degeneration in rdgA. They also suggest a key role for the lipid products of phosphoinositide hydrolysis in the activation of TRP channels in vivo.
Highlights
Transmembrane signalling cascades initiated by G-proteincoupled receptors are a widely used mechanism for signalling the detection of many sensory modalities
We show that InaD suppresses retinal degeneration A (rdgA) and that the rescue is correlated with reduced levels of phospholipase Cβ (PLCβ), a key enzyme for TRP channel activation
The results demonstrate a previously unknown requirement for a balance of PLCβ and diacylglycerol kinase (DGK) activity for retinal degeneration in rdgA
Summary
Transmembrane signalling cascades initiated by G-proteincoupled receptors are a widely used mechanism for signalling the detection of many sensory modalities These cascades end with the activation of plasma-membrane ion channels whose activity alters membrane potential and initiates synaptic transmission of a signal to the central nervous system. Members of the TRP family of ion channels have been implicated in the transduction of several sensory modalities in both vertebrate and invertebrate systems. These include light (Drosophila TRPC), pheromones (rodent TRPC2), taste (rodent TRPM), physical stimuli and temperature (Drosophila and mammal TRPV, TRPA and TRPN) (Montell et al, 2002). Only a few transduction components have been identified and the inability to perform in vivo analysis of channel activation has been a major obstacle in revealing how TRP channels are activated
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