Secreted Human Amyloid Precursor Protein Binds Semaphorin 3a and Prevents Semaphorin-Induced Growth Cone Collapse 英文参考文献.docVIP

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Secreted Human Amyloid Precursor Protein Binds Semaphorin 3a and Prevents Semaphorin-Induced Growth Cone Collapse 英文参考文献.doc

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Secreted Human Amyloid Precursor Protein Binds Semaphorin 3a and Prevents Semaphorin-Induced Growth Cone Collapse 英文参考文献

SecretedHumanAmyloidPrecursorProteinBinds Semaphorin3aandPreventsSemaphorin-Induced GrowthConeCollapse MargaretH.Magdesian1*.,MatthiasGralle1*.,LuizH.Guerreiro1,PauloJose′ I.Beltra?o1,MilenaM.V.F. Carvalho1,Lu?′sEduardodaS.Santos2,FernandoG.deMello2,RicardoA.M.Reis2,Se′rgioT.Ferreira1 1InstituteofMedicalBiochemistry,PrograminBiochemistryandCellularBiophysics,FederalUniversityofRiodeJaneiro,RiodeJaneiro,Brazil,2InstituteofBiophysics CarlosChagasFilho,PrograminNeurobiology,FederalUniversityofRiodeJaneiro,RiodeJaneiro,Brazil Abstract Theamyloidprecursorprotein(APP)iswellknownforgivingrisetotheamyloid-bpeptideandforitsroleinAlzheimer’s disease.Muchlessisknown,however,onthephysiological rolesofAPPinthedevelopment andplasticity ofthecentral nervoussystem.Wehaveusedphagedisplayofapeptidelibrarytoidentifyhigh-affinity ligandsofpurifiedrecombinant human sAPPa695 (the soluble, secreted ectodomain from the main neuronal APP isoform). Two peptides thus selected exhibited significant homologies withtheconservedextracellular domainofseveralmembersofthesemaphorin (Sema) family of axon guidance proteins. We show that sAPPa695 binds both purified recombinant Sema3A and Sema3A secreted bytransfected HEK293 cells. Interestingly, sAPPa695 inhibited the collapse ofembryonic chicken (Gallus gallus domesticus) dorsal root ganglia growth cones promoted by Sema3A (Kd#8?1029M). Two Sema3A-derived peptides homologous to the peptides isolated by phage display blocked sAPPa binding and its inhibitory action on Sema3A function. Thesetwopeptides arecomprised withinadomainpreviously showntobeinvolved inbinding ofSema3Ato its cellular receptor, suggesting a competitive mechanism by which sAPPa modulates the biological action of semaphorins. Citation:MagdesianMH,GralleM,GuerreiroLH,Beltra?o PJI,CarvalhoMMVF,etal.(2011)SecretedHumanAmyloidPrecursorProteinBindsSemaphorin3aand PreventsSemaphorin-InducedGrowthConeCollapse.PLoSONE6(7):e22857.doi:10.1371/journal.pone.0022857 E