Reduction of DILP2 in Drosophila Triages a Metabolic Phenotype from Lifespan Revealing Redundancy and Compensation among DILPs 英文参考文献.docVIP

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Reduction of DILP2 in Drosophila Triages a Metabolic Phenotype from Lifespan Revealing Redundancy and Compensation among DILPs 英文参考文献.doc

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Reduction of DILP2 in Drosophila Triages a Metabolic Phenotype from Lifespan Revealing Redundancy and Compensation among DILPs 英文参考文献

ReductionofDILP2inDrosophilaTriagesaMetabolic PhenotypefromLifespanRevealingRedundancyand CompensationamongDILPs SusanBroughton1.,NazifAlic1.,CathySlack1,TimothyBass1,TomoatsuIkeya1,GiovannaVinti1 ,Anna MariaTommasi1¤a,YasmineDriege1¤b,ErnstHafen2,LindaPartridge1* 1UCLInstituteofHealthyAgeing,GEE,UniversityCollegeLondon,London,UnitedKingdom,2ETHZurich,InstituteofMolecularSystemsBiology,Zurich,Switzerland Abstract Theinsulin/IGF-likesignalling(IIS)pathwayhasdiversefunctionsinallmulticellularorganisms,includingdeterminationof lifespan.Theseveninsulin-likepeptides(DILPs)inDrosophilaareexpressedinastage-andtissue-specificmanner.Partial ablation of the median neurosecretory cells (mNSCs) in the brain, which produce three DILPs, extends lifespan, reduces fecundity, alters lipid and carbohydrate metabolism and increases oxidative stress resistance. To determine if reduced expressionofDILPsiscausalintheseeffects,andtoinvestigatepossiblefunctionaldiversificationandredundancybetween DILPs,weusedRNAinterferencetolowerspecificallythetranscriptandproteinlevelsofdilp2,themosthighlyexpressedof themNSC-derivedDILPs.WefoundthatDILP2waslimitingonlyfortheincreasedwhole-bodytrehalosecontentassociated withmNSC-ablation.Weobservedacompensatoryincreaseindilp3and5mRNAupondilp2knockdown.Bymanipulation ofdfoxoanddInR,weshowedthattheincreaseindilp3isregulatedviaautocrineinsulinsignalinginthemNSCs.Ourstudy demonstrates that, despite the correlation between reduced dilp2 mRNA levels and lifespan-extension often observed, DILP2 reduction is not sufficient to extend lifespan. Nor is the increased trehalose storage associated with reduced IIS sufficient to extend lifespan. To understand the normal regulation of expression of the dilps and any functional diversificationbetweenthemwillrequireindependentcontroloftheexpressionofdifferentdilps. Citation: BroughtonS,AlicN,SlackC,BassT,IkeyaT,etal.(2008)ReductionofDILP2in DrosophilaTriages aMetabolicPhenotypefromLifespanRevealing Redundancyand