Signaling Logic of Activity-Triggered Dendritic Protein Synthesis An mTOR Gate But Not a Feedback Switch 英文参考文献.docVIP

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Signaling Logic of Activity-Triggered Dendritic Protein Synthesis An mTOR Gate But Not a Feedback Switch 英文参考文献.doc

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Signaling Logic of Activity-Triggered Dendritic Protein Synthesis An mTOR Gate But Not a Feedback Switch 英文参考文献

SignalingLogicofActivity-TriggeredDendriticProtein Synthesis:AnmTORGateButNotaFeedbackSwitch PragatiJain,UpinderS.Bhalla* NationalCentreforBiologicalSciences,TataInstituteofFundamentalResearch,Bangalore,India Abstract Changesinsynapticefficacyarebelievedtoformthecellularbasisformemory.Proteinsynthesisindendritesisneededto consolidatelong-termsynapticchanges.Manysignalsconvergetoregulatedendriticproteinsynthesis,includingsynaptic and cellular activity, and growth factors. The coordination of these multiple inputs is especially intriguing because the syntheticandcontrolpathwaysthemselvesareamongthesynthesizedproteins.Wehavemodeledthissystemtostudyits molecularlogicandtounderstandhowrunawayfeedbackisavoided.Weshowthatgrowthfactorssuchasbrain-derived neurotrophicfactor(BDNF)gateactivity-triggeredproteinsynthesisviamammaliantargetofrapamycin(mTOR).Wealso showthatbistabilityisunlikelytoarisefromthemajorproteinsynthesispathwaysinourmodel,eventhoughtheseinclude several positive feedback loops. We propose that these gating and stability properties may serve to suppress runaway activationofthepathway,whilepreservingthekeyroleofresponsivenesstomultiplesourcesofinput. Citation: JainP,BhallaUS(2009)SignalingLogicofActivity-Triggered Dendritic ProteinSynthesis:AnmTOR GateBut NotaFeedbackSwitch.PLoSComput Biol5(2):e1000287.doi:10.1371/journal.pcbi.1000287 Editor:KarlJ.Friston,UniversityCollegeLondon,UnitedKingdom ReceivedOctober14,2008;AcceptedJanuary5,2009;PublishedFebruary13,2009 Copyright: ? 2009 Jain, Bhalla. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbyDAE/SRCandbyDBT,India.PJwassupportedbyagrantfromtheEU-IndiaGridproject. CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist. *E-mail:bhalla@ncbs.res.in Introduction neurotransmitters such as glutamat