SLOB, a SLOWPOKE Channel Binding Protein, Regulates Insulin Pathway Signaling and Metabolism in Drosophila 英文参考文献.docVIP

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SLOB, a SLOWPOKE Channel Binding Protein, Regulates Insulin Pathway Signaling and Metabolism in Drosophila 英文参考文献.doc

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SLOB, a SLOWPOKE Channel Binding Protein, Regulates Insulin Pathway Signaling and Metabolism in Drosophila 英文参考文献

SLOB,aSLOWPOKEChannelBindingProtein,Regulates InsulinPathwaySignalingandMetabolisminDrosophila AmandaL.Sheldon,JiamingZhang,HongFei,IrwinB.Levitan* DepartmentofNeuroscience,ThomasJeffersonUniversity,Philadelphia,Pennsylvania,UnitedStatesofAmerica Abstract Thereisampleevidencethationchannelmodulationbyaccessoryproteinswithinamacromolecularcomplexcanregulate channel activity and thereby impact neuronal excitability. However, the downstream consequences of ion channel modulation remain largely undetermined. The Drosophila melanogaster large conductance calcium-activated potassium channelSLOWPOKE(SLO)undergoesmodulationviaitsbindingpartnerSLO-bindingprotein(SLOB).RegulationofSLOby SLOB influences the voltage dependence of SLO activation and modulates synaptic transmission. SLO and SLOB are expressedespeciallyprominentlyinmedianneurosecretorycells(mNSCs)intheparsintercerebralis(PI)regionofthebrain; these cells also express and secrete Drosophila insulin like peptides (dILPs). Previously, we found that flies lacking SLOB exhibit increased resistance to starvation, and we reasoned that SLOB may regulate aspects of insulin signaling and metabolism. Here we investigate the role of SLOB in metabolism and find that slob null flies exhibit changes in energy storage and insulin pathway signaling. In addition, slob null flies have decreased levels of dilp3 and increased levels of takeout,ageneknowntobeinvolvedinfeedingandmetabolism.TargetedexpressionofSLOBtomNSCsrescuesthese alterations in gene expression, as well as the metabolic phenotypes. Analysis of fly lines mutant for both slob and slo indicatethattheeffectofSLOBonmetabolismandgeneexpressionisviaSLO.WeproposethatmodulationofSLObySLOB regulatesneurotransmissioninmNSCs,influencingdownstreaminsulinpathwaysignalingandmetabolism. Citation: SheldonAL,ZhangJ,FeiH, LevitanIB (2011)SLOB, aSLOWPOKEChannelBinding Protein, Regulates Insulin PathwaySignaling andMetabolismin Drosophila.PLoSONE6(8):e23343.doi:10.1371/journal.pone.