Systematic discovery of Rab GTPases with synaptic functions in Drosophila
1704 - 1715
Item Usage Stats
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.
Rab27 protein, Drosophila
bacterial artificial chromosome
gene expression regulation
Animals, Genetically Modified
Chromosomes, Artificial, Bacterial
Gene Expression Regulation, Enzymologic
Gene Knockout Techniques
rab GTP-Binding Proteins
Published Version (Please cite this version)http://dx.doi.org/10.1016/j.cub.2011.08.058
Showing items related by title, author, creator and subject.
TRIB2 confers resistance to anti-cancer therapy by activating the serine/threonine protein kinase AKT Hill, R.; Madureira, P. A.; Ferreira, B.; Baptista, I.; Machado, S.; Colaço, L.; Dos Santos, M.; Liu, N.; Dopazo, A.; Ugurel, S.; Adrienn, A.; Kiss-Toth, E.; Isbilen, M.; Gure, A. O.; Link, W. (Nature Publishing Group, 2017)Intrinsic and acquired resistance to chemotherapy is the fundamental reason for treatment failure for many cancer patients. The identification of molecular mechanisms involved in drug resistance or sensitization is imperative. ...
Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: A novel gene related to nuclear envelopathies Kayman-Kurekci G.; Talim, B.; Korkusuz P.; Sayar, N.; Sarioglu, T.; Oncel I.; Sharafi P.; Gundesli H.; Balci-Hayta, B.; Purali, N.; Serdaroglu-Oflazer P.; Topaloglu H.; Dincer P. (Elsevier Ltd, 2014)We performed genome-wide homozygosity mapping and mapped a novel myopathic phenotype to chromosomal region 1q25 in a consanguineous family with three affected individuals manifesting proximal and distal weakness and atrophy, ...
Protein folding, misfolding and aggregation: the importance of two-electron stabilizing interactions Cieplak, A. S. (Public Library of Science, 2017)Proteins associated with neurodegenerative diseases are highly pleiomorphic and may adopt an all-α-helical fold in one environment, assemble into all-β-sheet or collapse into a coil in another, and rapidly polymerize in ...