Article

Photomechanical responses in Drosophila photoreceptors.

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
Science (Impact Factor: 31.48). 10/2012; 338(6104):260-3. DOI: 10.1126/science.1222376
Source: PubMed

ABSTRACT 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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    ABSTRACT: EC#coupling#is#subjected#to#a# mechanical#feedback,#which#originates#from# physical#force;sensing#ion#channels in#the# pericardium#and#elsewhere.##Reviewed#here# are#the#most recent developments#that# greatly#advanced our#understanding#of# these#mechanosensitive#(MS)#channels,# including#TRPs#and#K2p’s.##Patch#clamp#has# continued#to#demonstrate#the direct#channel# activation#by#membrane#stretch.## Crystallography#and#cryo;electron# microscopy#have#revealed#the#structures#of# several#MS#channels#at#atomic#resolution.## Some#have#been#purified#to#homogeneity,# reconstituted#into#lipid#bilayer,#and#still# retain#their#ability#to#respond#to#stretch#force.## A#force;from;lipid#(FFL)#theory#has#been# advanced#that#emphasizes#the#strong# binding#between#channel#proteins and lipids.## Through#these#bonds,#the#sharp#lateral# tension#(akin#to#surface#tension)#of#the# bilayer#can#transmit#added#force to#the# channel protein.##Like#temperature# sensitivity,#sensitivity#to#mechanical#force#is# far#more#pervasive than#we#previously# realize,#and#is#especially#important#to#the#beating#heart
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    ABSTRACT: Drosophila phototransduction is mediated via a G-protein-coupled PLC cascade. Recent evidence, including the demonstration that light evokes rapid contractions of the photoreceptors, suggested that the light-sensitive channels (TRP and TRPL) may be mechanically gated, together with protons released by PLC-mediated PIP2 hydrolysis. If mechanical gating is involved we predicted that the response to light should be influenced by altering the physical properties of the membrane. To achieve this, we used diet to manipulate the degree of saturation of membrane phospholipids. In flies reared on a yeast diet, lacking polyunsaturated fatty acids (PUFAs), mass spectrometry showed that the proportion of polyunsaturated phospholipids was sevenfold reduced (from 38 to ∼5%) but rescued by adding a single species of PUFA (linolenic or linoleic acid) to the diet. Photoreceptors from yeast-reared flies showed a 2- to 3-fold increase in latency and time to peak of the light response, without affecting quantum bump waveform. In the absence of Ca(2+) influx or in trp mutants expressing only TRPL channels, sensitivity to light was reduced up to ∼10-fold by the yeast diet, and essentially abolished in hypomorphic G-protein mutants (Gαq). PLC activity appeared little affected by the yeast diet; however, light-induced contractions measured by atomic force microscopy or the activation of ectopic mechanosensitive gramicidin channels were also slowed ∼2-fold. The results are consistent with mechanosensitive gating and provide a striking example of how dietary fatty acids can profoundly influence sensory performance in a classical G-protein-coupled signaling cascade. Copyright © 2015 Randall et al.
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    ABSTRACT: The mammalian brain is a mechanosensitive organ that responds to different mechanical forces ranging from intrinsic forces implicated in brain morphogenesis to extrinsic forces that can cause concussion and traumatic brain injury. However, little is known of the mechanosensors that transduce these forces. In this study we use cell-attached patch recording to measure single mechanically-gated (MG) channel currents and their affects on spike activity in identified neurons in neonatal mouse brain slices. We demonstrate that both neocortical and hippocampal pyramidal neurons express stretch-activated MG cation channels that are activated by suctions of~25mm Hg, have a single channel conductance for inward current of 50-70pS and show weak selectivity for alkali metal cations (i.e., Na(+)<K(+)<Cs(+)). Significantly, single MG channel currents activated on the soma trigger spiking/action potentials in both neocortical and hippocampal pyramidal neurons. Not all neuron types studied here expressed MG channel currents. In particular, locus coeruleus and cerebellar Purkinje neurons showed no detectable MG channel activity. Moreover their robust rhythmic spike activity was resistant to mechanical modulation. Our observation that a single MG channel current can trigger spiking predicates the need for reassessment of the long held view that the impulse output of central neurons depends only upon their intrinsic voltage-gated channels and/or their integrated synaptic input. Copyright © 2015. Published by Elsevier B.V.

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