Regulation of Drosophila TRP channels by lipid messengers.
In common with their vertebrate homologues, the prototypical Drosophila TRP channels are activated downstream of phospholipase C (PLC) by unknown mechanism(s). Most recent evidence in Drosophila photoreceptors now indicates that excitation is mediated, not by inositol 1,4,5-trisphosphate (IP3), but by lipid products of PLC action, such as diacylglycerol (DAG), its metabolites (polyunsaturated fatty acids, PUFAs), or the reduction in phosphatidylinositol 4,5-bisphosphate (PIP2). Compelling evidence for a PKC independent role of DAG comes from mutants of the rdgA gene, which encodes DAG kinase. The rdgA mutation leads to constitutive activation of both TRP and TRPL channels and dramatically increases sensitivity to light in hypomorphic mutations of PLC or G protein. A role for PIP2 reduction is suggested by finding that conditions, which lead to acute PIP2 depletion--monitored by genetically targeted PIP2-sensitive ion channels--also lead to constitutive activation of TRP channels. Finally, recent data indicate that PUFAs activate TRP channels directly, and independently of PLC or metabolic inhibition. Together with evidence from several mammalian TRP homologues, these results suggest that regulation by lipids may be a defining feature of many TRP channels.
Hardie
Roger C
RC
Cambridge University Department of Anatomy, Downing Street, Cambridge CB2 3DY, UK.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*; D050052:TRPC Cation Channels; D050051:Transient Receptor Potential Channels; D014785:Vision, Ocular / Q000502:physiology*
D015220:Calcium Channels; D004075:Diglycerides; D029721:Drosophila Proteins; D005231:Fatty Acids, Unsaturated; D019269:Phosphatidylinositol 4,5-Diphosphate; D050052:TRPC Cation Channels; D050051:Transient Receptor Potential Channels; C063169:trp protein, Drosophila; D002118:Calcium