ThesignaltransductioncascaderesponsIBLeforsensinglightinvertebratesisoneofthebeststudiedsignaltransductionprocesses,andisinitiatedbyrhodopsininrodcells,amemberoftheG-proteincoupledreceptorgenefamily.RhodopsinremainstheonlyGPCRwhosestructurehasbeenresolvedathighresolution.Rhodopsininthediscsofrodcellscontainsabound11-cisretinalchromophore,asmallmoleculederivedfromVitaminAthatactsasthelightsensitiveportionofthereceptormolecule,absorbinglighttoinitiatethesignaltransductioncascade.Whenlightstrikes11-cisretinalandisabsorbed,itisomerizestoall-transretinal,changingtheshapeofthemoleculeandthereceptoritisboundto.Thischangeinrhodopsin’sshapealtersitsinteractionwithtransducin,thememberoftheG-proteingenefamilythatisspecificinitsroleinvisualsignaltransduction.ActivationoftransducincausesitsalphasubunittodissociatefromthetrimerandexchangeboundGDPforGTP,activatinginturnamembrane-boundcyclic-GMPspecificphosphodiesterasethathydrolyzescGMP.Intherestingrodcell,highlevelsofcGMPassociatewithacyclic-GMPgatedsodiumchannelintheplasmamembrane,keepingthechannelsopenandthemembraneoftherestingrodcellsdepolarized.Thisisdistinctfromsynapticgenerationofactionpotentials,inwhichstimulationinducesopeningofsodiumchannelsanddepolarization.WhencGMPgatedchannelsinrodcellsopen,bothsodiumandcalciumionsenterthecell,hyperpolarizingthemembraneandinitiatingtheelectRochemicalimpulseresponsibleforconveyingthesignalfromthesensoryneurontotheCNS.Therodcellintherestingstatereleaseshighlevelsoftheinhibitoryneurotransmitterglutamate,whilethereleaseofglutamateisrepressedbythehyperpolarizationinthepresenceoflighttotriggeradownstreamactionpotentialbyganglioncellsthatconveysignalstothebrain.ThecalciumwhichentersthecellalsoactivatesGCAP,whichactivatesguanylatecyclase(GC-1andGC-2)torapidlyproducemorecGMP,endingthehyperpolarizationandreturningthecelltoitsrestingdepolarizedstate.Aproteincalledrecoverinhelpsmediatetheinactivationofthesignaltransductioncascade,returningrhodopsintoitspreactivatedstate,alongwiththerhodopsinkinaseGrk1.PhosphorylationofrhodopsinbyGrklcausesarrestintobind,helpingtoterminatethereceptoractivationsignal.Dissociationandreassociationofretinal,dephosphorylationofrhodopsinandreleaseofarrestinallreturnrhodopsintoitsreadystate,preparedonceagaintorespondtolight.

Contributor:GlennCroston,PhD

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