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      Systematic discovery of Rab GTPases with synaptic functions in Drosophila

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      Author
      Chan, C.-C.
      Scoggin, S.
      Wang, D.
      Cherry, S.
      Dembo, T.
      Greenberg, B.
      Jin, E.J.
      Kuey, C.
      Lopez, A.
      Mehta, S.Q.
      Perkins, T.J.
      Brankatschk, M.
      Rothenfluh, A.
      Buszczak, M.
      Hiesinger P.R.
      Date
      2011
      Source Title
      Current Biology
      Print ISSN
      0960-9822
      Volume
      21
      Issue
      20
      Pages
      1704 - 1715
      Language
      English
      Type
      Article
      Item Usage Stats
      154
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      88
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      Abstract
      Background: 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.
      Keywords
      Drosophila protein
      Rab protein
      Rab27 protein, Drosophila
      animal
      antibody specificity
      article
      bacterial artificial chromosome
      brain
      Drosophila
      gene expression regulation
      gene inactivation
      genetics
      homologous recombination
      metabolism
      multigene family
      mutation
      nerve cell
      phenotype
      physiology
      synapse
      transgenic animal
      Animals
      Animals, Genetically Modified
      Brain
      Chromosomes, Artificial, Bacterial
      Drosophila
      Drosophila Proteins
      Gene Expression Regulation, Enzymologic
      Gene Knockout Techniques
      Homologous Recombination
      Multigene Family
      Mutation
      Neurons
      Organ Specificity
      Phenotype
      rab GTP-Binding Proteins
      Synapses
      Permalink
      http://hdl.handle.net/11693/21745
      Published Version (Please cite this version)
      http://dx.doi.org/10.1016/j.cub.2011.08.058
      Collections
      • Department of Molecular Biology and Genetics 442
      • Department of Psychology 167
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