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dc.contributor.authorChan, C.-C.en_US
dc.contributor.authorScoggin, S.en_US
dc.contributor.authorWang, D.en_US
dc.contributor.authorCherry, S.en_US
dc.contributor.authorDembo, T.en_US
dc.contributor.authorGreenberg, B.en_US
dc.contributor.authorJin, E.J.en_US
dc.contributor.authorKuey, C.en_US
dc.contributor.authorLopez, A.en_US
dc.contributor.authorMehta, S.Q.en_US
dc.contributor.authorPerkins, T.J.en_US
dc.contributor.authorBrankatschk, M.en_US
dc.contributor.authorRothenfluh, A.en_US
dc.contributor.authorBuszczak, M.en_US
dc.contributor.authorHiesinger P.R.en_US
dc.date.accessioned2016-02-08T09:50:36Z
dc.date.available2016-02-08T09:50:36Z
dc.date.issued2011en_US
dc.identifier.issn0960-9822
dc.identifier.urihttp://hdl.handle.net/11693/21745
dc.description.abstractBackground: Neurons require highly specialized intracellular membrane trafficking, especially at synapses. Rab GTPases are considered master regulators of membrane trafficking in all cells, and only very few Rabs have known neuron-specific functions. Here, we present the first systematic characterization of neuronal expression, subcellular localization, and function of Rab GTPases in an organism with a brain. Results: We report the surprising discovery that half of all Drosophila Rabs function specifically or predominantly in distinct subsets of neurons in the brain. Furthermore, functional profiling of the GTP/GDP-bound states reveals that these neuronal Rabs are almost exclusively active at synapses and the majority of these synaptic Rabs specifically mark synaptic recycling endosomal compartments. Our profiling strategy is based on Gal4 knockins in large genomic fragments that are additionally designed to generate mutants by ends-out homologous recombination. We generated 36 large genomic targeting vectors and transgenic rab-Gal4 fly strains for 25 rab genes. Proof-of-principle knockout of the synaptic rab27 reveals a sleep phenotype that matches its cell-specific expression. Conclusions: Our findings suggest that up to half of all Drosophila Rabs exert specialized synaptic functions. The tools presented here allow systematic functional studies of these Rabs and provide a method that is applicable to any large gene family in Drosophila. © 2011 Elsevier Ltd. All rights reserved.en_US
dc.language.isoEnglishen_US
dc.source.titleCurrent Biologyen_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cub.2011.08.058en_US
dc.subjectDrosophila proteinen_US
dc.subjectRab proteinen_US
dc.subjectRab27 protein, Drosophilaen_US
dc.subjectanimalen_US
dc.subjectantibody specificityen_US
dc.subjectarticleen_US
dc.subjectbacterial artificial chromosomeen_US
dc.subjectbrainen_US
dc.subjectDrosophilaen_US
dc.subjectgene expression regulationen_US
dc.subjectgene inactivationen_US
dc.subjectgeneticsen_US
dc.subjecthomologous recombinationen_US
dc.subjectmetabolismen_US
dc.subjectmultigene familyen_US
dc.subjectmutationen_US
dc.subjectnerve cellen_US
dc.subjectphenotypeen_US
dc.subjectphysiologyen_US
dc.subjectsynapseen_US
dc.subjecttransgenic animalen_US
dc.subjectAnimalsen_US
dc.subjectAnimals, Genetically Modifieden_US
dc.subjectBrainen_US
dc.subjectChromosomes, Artificial, Bacterialen_US
dc.subjectDrosophilaen_US
dc.subjectDrosophila Proteinsen_US
dc.subjectGene Expression Regulation, Enzymologicen_US
dc.subjectGene Knockout Techniquesen_US
dc.subjectHomologous Recombinationen_US
dc.subjectMultigene Familyen_US
dc.subjectMutationen_US
dc.subjectNeuronsen_US
dc.subjectOrgan Specificityen_US
dc.subjectPhenotypeen_US
dc.subjectrab GTP-Binding Proteinsen_US
dc.subjectSynapsesen_US
dc.titleSystematic discovery of Rab GTPases with synaptic functions in Drosophilaen_US
dc.typeArticleen_US
dc.departmentDepartment of Psychology
dc.departmentDepartment of Molecular Biology and Genetics
dc.citation.spage1704en_US
dc.citation.epage1715en_US
dc.citation.volumeNumber21en_US
dc.citation.issueNumber20en_US
dc.identifier.doi10.1016/j.cub.2011.08.058en_US


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