Systematic discovery of Rab GTPases with synaptic functions in Drosophila
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
2011Source Title
Current Biology
Print ISSN
0960-9822
Volume
21
Issue
20
Pages
1704 - 1715
Language
English
Type
ArticleItem Usage Stats
154
views
views
88
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downloads
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 proteinRab 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/11693/21745Published Version (Please cite this version)
http://dx.doi.org/10.1016/j.cub.2011.08.058Collections
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