Polyunsaturated fatty acids activate the Drosophila light-sensitive channels TRP and TRPL

Chyb, Sylwester; Raghu, Padinjat; Hardie, Roger C.

doi:10.1038/16703

Cited by 371 publications

(297 citation statements)

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“…DAG, is blocked. This massive facilitation underscores other recent evidence indicating that DAG or a downstream metabolite is the essential messenger of excitation in Drosophila phototransduction (6,7,17).…”

Section: Discussionmentioning

confidence: 78%

“…By a still unknown mechanism, this process activates at least two classes of light-sensitive channels in the microvilli, encoded by the transient receptor potential (trp) and trp-like (trpl) genes, which are the prototypical members of the large TRP ion channel superfamily (4,5). Recent evidence suggests that lipid products of PIP 2 hydrolysis are the messengers of excitation (6,7), but this is still a subject of controversy (3, 8 -10).…”

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confidence: 99%

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Rescue of Light Responses in the Drosophila “Null” Phospholipase C Mutant, norpA, by the Diacylglycerol Kinase Mutant, rdgA, and by Metabolic Inhibition

Hardie

Martín

Chyb³

et al. 2003

Journal of Biological Chemistry

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Light responses in Drosophila are reportedly abolished in severe mutants of the phospholipase C (PLC) gene, norpA. However, on establishing the whole-cell recording configuration in photoreceptors of the supposedly null allele, norpA P24 , we detected a small (ϳ15 pA) inward current that represented spontaneous light channel activity. The current decayed during ϳ20 min, after which tiny residual responses (<2 pA) were elicited by intense flashes. Both spontaneous currents and light responses appeared to be mediated by residual PLC activity, because they were enhanced by impairing diacylglycerol (DAG) kinase function by mutation (rdgA) or by restricting ATP but were reduced or abolished by a mutation of the PLC-specific G q ␣ subunit. It was reported recently that metabolic inhibition activated the light-sensitive transient receptor potential and transient receptor potential-like channels, even in norpA P24 , leading to the conclusion that this action was independent of PLC (Agam, K., von Campenhausen, M., Levy, S., Ben-Ami, H. C., Cook, B., Kirschfeld, K., and Minke, B. (2000) J. Neurosci. 20, 5748 -5755). However, we found that channel activation by metabolic inhibitors in norpA P24 was strictly dependent on the residual PLC activity underlying the spontaneous current, because the inhibitors failed to activate any channels after the spontaneous current had decayed. By contrast, polyunsaturated fatty acids invariably activated the channels independently of PLC. The results strongly support the obligatory requirement for PLC and DAG in Drosophila phototransduction, suggest that activation by metabolic inhibition is primarily because of the failure of diacylglycerol kinase, and are consistent with the proposal that polyunsaturated fatty acids, which are potential DAG metabolites, act directly on the channels.

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Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 99%

Rescue of Light Responses in the Drosophila “Null” Phospholipase C Mutant, norpA, by the Diacylglycerol Kinase Mutant, rdgA, and by Metabolic Inhibition

Hardie

Martín

Chyb³

et al. 2003

Journal of Biological Chemistry

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“…In support of this conclusion, introduction of either DAG or PUFAs, such as linolenic acid, results in activation of the channels in photoreceptor cells or in vitro [148]. The channels are constitutively active in the rdgA mutant, which is missing the DAG kinase that metabolizes DAG to PA [136].…”

Section: The Trpc Cation Channelsmentioning

confidence: 78%

Phototransduction and retinal degeneration in Drosophila

Wang

Montell

2007

Pflugers Arch - Eur J Physiol

257

303

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Drosophila visual transduction is the fastest known G-protein-coupled signaling cascade and has therefore served as a genetically tractable animal model for characterizing rapid responses to sensory stimulation. Mutations in over 30 genes have been identified, which affect activation, adaptation, or termination of the photoresponse. Based on analyses of these genes, a model for phototransduction has emerged, which involves phosphoinoside signaling and culminates with opening of the TRP and TRPL cation channels. Many of the proteins that function in phototransduction are coupled to the PDZ containing scaffold protein INAD and form a supramolecular signaling complex, the signalplex. Arrestin, TRPL, and Gα q undergo dynamic light-dependent trafficking, and these movements function in long-term adaptation. Other proteins play important roles either in the formation or maturation of rhodopsin, or in regeneration of phosphatidylinositol 4,5-bisphosphate (PIP 2 ), which is required for the photoresponse. Mutation of nearly any gene that functions in the photoresponse results in retinal degeneration. The underlying bases of photoreceptor cell death are diverse and involve mechanisms such as excessive endocytosis of rhodopsin due to stable rhodopsin/arrestin complexes and abnormally low or high levels of Ca 2+ . Drosophila visual transduction appears to have particular relevance to the cascade in the intrinsically photosensitive retinal ganglion cells in mammals, as the photoresponse in these latter cells appears to operate through a remarkably similar mechanism.

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“…Mutant flies that lack the IP 3 receptor gene remain capable of generating normal sustained receptor potentials on continuous light exposure (65). It is now believed that Drosophila TRP proteins are activated by DAG, polyunsaturated fatty acids (downstream metabolites of DAG), and/or a reduction of phosphatidylinositol 4,5-bisphosphate 2 (66,67). Thus, the question of whether and which TRP constitutes SOC remains unsettled.…”

Section: Role Of Trp In Plc-dependent Ca 2ϩ Influxmentioning

confidence: 99%

The Transient Receptor Potential Superfamily of Ion Channels

Huang

2004

Journal of the American Society of Nephrology

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Abstract. The transient receptor potential (TRP) superfamily of proteins is cation-selective ion channels with six predicted transmembrane segments and intracellularly localized amino and carboxyl termini. Members of the TRP superfamily are identified on the basis of amino acid sequence and structural similarity and are classified into TRPC, TRPV, TRPM, TRPP, TRPN, and TRPML subfamilies. TRP channels are widespread and have diverse functions, ranging from thermal, tactile, taste, osmolar, and fluid flow sensing to transepithelial Ca 2ϩ and Mg 2ϩ transport. Mutations of TRP proteins produce many renal diseases, including Mg 2ϩ wasting, hypocalcemia, and polycystic kidney diseases. This review focuses on recent advances in the understanding of their functions.The first transient receptor potential (TRP) protein was discovered in studies that examined Drosophila phototransduction (1). The photoreceptor cells of Drosophila exhibit sustained receptor potentials in response to continuous light exposure. The ionic basis for the sustained receptor potentials is influx of Ca 2ϩ from the extracellular space. Cosens and Manning (1) reported in 1969 that one group of mutant flies exhibits TRP upon continuous light exposure and named it trp, for transient receptor potential. The trp gene was cloned in 1989 (2) and subsequently shown to encode a Ca 2ϩ -permeable cation channel (3). Since then, many channels that bear sequence and structural similarities to the Drosophila TRP have been cloned from flies, worms, and mammals. Together, they form the TRP superfamily.Ion channels (e.g., voltage-gated K ϩ channels) are typically identified by their modes of activation and/or ion selectivity. Each family or superfamily of ion channels of similar activation and selectivity consists of multiple members of channel proteins with amino acid sequence homology. Unlike most ion channel families, the TRP superfamily of ion channels are identified on the basis of homology only. The mode of activation and selectivity for TRP channels are disparate. Some TRP channels are activated by ligands, whereas others are regulated by physical stimuli (e.g., heat) or yet-unknown mechanisms. All TRP channels are cation selective, but the selectivity ratio for Ca 2ϩ versus the monovalent cation Na ϩ (P Ca /P Na ) varies widely, ranging from Ͼ100:1, to 1 to 10:1, to Ͻ0.05:1. The lack of common identifying features has in part contributed to the confusing nomenclature of TRP channels in the literature.A recent consensus report proposed a unified nomenclature for the TRP superfamily (4). It classified TRP channels into TRPC, TRPV, and TRPM subfamilies. More recent classification has expanded TRP superfamily to include three additional, more distantly related subfamilies, TRPP, TRPML, and TRPN ( Figure 1). Structurally, all of these TRP channels have six predicted transmembrane (TM) segments and N-terminal and C-terminal cytoplasmic tails similar to topologies of voltagegated K ϩ , Na ϩ , and Ca 2ϩ channels; cyclic nucleotide-gated channels; and hyperpolarizati...

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Polyunsaturated fatty acids activate the Drosophila light-sensitive channels TRP and TRPL

Cited by 371 publications

References 29 publications

Rescue of Light Responses in the Drosophila “Null” Phospholipase C Mutant, norpA, by the Diacylglycerol Kinase Mutant, rdgA, and by Metabolic Inhibition

Rescue of Light Responses in the Drosophila “Null” Phospholipase C Mutant, norpA, by the Diacylglycerol Kinase Mutant, rdgA, and by Metabolic Inhibition

Phototransduction and retinal degeneration in Drosophila

The Transient Receptor Potential Superfamily of Ion Channels

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