Photomechanical Responses in Drosophila Photoreceptors

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
Science (Impact Factor: 33.61). 10/2012; 338(6104):260-3. DOI: 10.1126/science.1222376
Source: PubMed


Phototransduction in Drosophila microvillar photoreceptor cells is mediated by a G protein-activated phospholipase C (PLC). PLC hydrolyzes the minor membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP(2)), leading by an unknown mechanism to activation of the prototypical transient receptor potential (TRP) and TRP-like (TRPL) channels. We found that light exposure evoked rapid PLC-mediated contractions of the photoreceptor cells and modulated the activity of mechanosensitive channels introduced into photoreceptor cells. Furthermore, photoreceptor light responses were facilitated by membrane stretch and were inhibited by amphipaths, which alter lipid bilayer properties. These results indicate that, by cleaving PIP(2), PLC generates rapid physical changes in the lipid bilayer that lead to contractions of the microvilli, and suggest that the resultant mechanical forces contribute to gating the light-sensitive channels.

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Available from: Roger C Hardie, Oct 05, 2015
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    • "Physical properties of PR membranes are important as structural parameters, but they are also important for signaling. In Drosophila, upon light exposure, the cleavage of the minor lipid membrane phosphatidylinositol 4,5-bisphosphate (PIP2) by the NORPA phospholipase C (PLC) leads to a contraction of the rhabdomere, which is able to activate mechanosensitive channels [76]. Lipid composition of PR membrane is therefore essential to anchor and regulate the activity of proteins involved in phototransduction. "
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    ABSTRACT: The dysregulation of lipid metabolism has been implicated in various diseases, including diabetes, cardiopathies, dermopathies, retinal and neurodegenerative diseases. Mouse models have provided insights into lipid metabolism. However, progress in the understanding of these pathologies is hampered by the multiplicity of essential cellular processes and genes that modulate lipid metabolism. Drosophila and C. elegans have emerged as simple genetic models to improve our understanding of these metabolic diseases. Recent studies have characterized fatty acid transport protein (fatp) mutants in Drosophila and C. elegans, establishing new models of cardiomyopathy, retinal degeneration, fat storage disease and dermopathies. These models have generated novel insights into the physiological role of the Fatp protein family in vivo in multicellular organisms, and are likely to contribute substantially to progress in understanding the etiology of various metabolic disorders. Here, we describe and discuss the mechanisms underlying invertebrate fatp mutant models in the light of the current knowledge relating to FATPs and lipid disorders in vertebrates.
    Progress in lipid research 09/2015; DOI:10.1016/j.plipres.2015.08.001 · 10.02 Impact Factor
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    • "In Drosophila, photon absorption by rhodopsin causes photoisomerization to metarhodopsin, which activates a heterotrimeric Gq-protein, initiating a cascade leading to activation of IP 3 and diacylglycerol. Linkages from this cascade to opening of transient receptor potential (dTRP) and TRP-like (dTRPL) ion channels that carry the receptor current are still debated, and both chemical (Chyb et al., 1999; Huang et al., 2010) and mechanical (Hardie and Franze, 2012) intermediate steps have been proposed. In Drosophila, dTRP and dTRPL channels are thought to carry approximately equal parts of light-activated current under physiological conditions (Reuss et al., 1997). "
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    ABSTRACT: Our current understanding of insect phototransduction is based on a small number of species, but insects occupy many different visual environments. We created the retinal transcriptome of a nocturnal insect, the cockroach, Periplaneta americana to identify proteins involved in the earliest stages of compound eye phototransduction, and test the hypothesis that different visual environments are reflected in different molecular contributions to function. We assembled five novel mRNAs: two green opsins, one UV opsin, and one each TRP and TRPL ion channel homologs. One green opsin mRNA (pGO1) was 100-1000 times more abundant than the other opsins (pGO2 and pUVO), while pTRPL mRNA was 10 times more abundant than pTRP, estimated by transcriptome analysis or quantitative PCR (qPCR). Electroretinograms were used to record photoreceptor responses. Gene-specific in vivo RNA interference (RNAi) was achieved by injecting long (596-708 bp) double-stranded RNA into head hemolymph, and verified by qPCR. RNAi of the most abundant green opsin reduced both green opsins by more than 97% without affecting UV opsin, and gave a maximal reduction of 75% in ERG amplitude 7 days after injection that persisted for at least 19 days. RNAi of pTRP and pTRPL genes each specifically reduced the corresponding mRNA by 90%. Electroretinogram (ERG) reduction by pTRPL RNAi was slower than for opsin, reaching 75% attenuation by 21 days, without recovery at 29 days. pTRP RNAi attenuated ERG much less; only 30% after 21 days. Combined pTRP plus pTRPL RNAi gave only weak evidence of any cooperative interactions. We conclude that silencing retinal genes by in vivo RNAi using long dsRNA is effective, that visible light transduction in Periplaneta is dominated by pGO1, and that pTRPL plays a major role in cockroach phototransduction.
    Frontiers in Physiology 08/2015; 6:207. DOI:10.3389/fphys.2015.00207 · 3.53 Impact Factor
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    • "light-induced activation of a known MSC, gramicidin, introduced in photoreceptor cells in place of TRP and TRPL [48]. "
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    ABSTRACT: Transient receptor potential (TRP) proteins are cation channels that comprise a superfamily of molecular sensors that enable animals to detect a wide variety of environmental stimuli. This versatility enables vertebrate and invertebrate TRP channels to function in a diversity of senses, ranging from vision to taste, smell, touch, hearing, proprioception and thermosensation. Moreover, many individual TRP channels are activated through a surprising range of sensory stimuli. The multitasking nature of TRP channels raises the question as to whether seemingly disparate activators gate TRPs through common strategies. In this regard, a recent major advance is the discovery that a phospholipase C (PLC)-dependent signaling cascade activates the TRP channels in Drosophila photoreceptor cells through generation of force in the lipid-bilayer. The premise of this review is that mechanical force is a unifying, common strategy for gating TRP channels. In addition to several TRP channels that function in mechanosensation and are gated by force applied to the cells, changes in temperature or alterations in the concentration of lipophilic second messengers through stimulation of signaling cascades, cause architectural modifications of the cell membrane, which in turn activate TRP channels through mechanical force. Consequently, TRPs are capable of functioning as stretch-activated channels, even in cases in which the stimuli that initiate the signaling cascades are not mechanical. We propose that most TRPs are actually mechanosensitive channels (MSCs), which undergo conformational changes in response to tension imposed on the lipid bilayer, resulting in channel gating. Copyright © 2015 Elsevier Inc. All rights reserved.
    Biochemical and Biophysical Research Communications 04/2015; 460(1):22-25. DOI:10.1016/j.bbrc.2015.02.067 · 2.30 Impact Factor
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