Drosophila S2 cells secrete wingless on exosome-like vesicles but the wingless gradient forms independently of exosomes. 2013

Karen Beckett, and Solange Monier, and Lucy Palmer, and Cyrille Alexandre, and Hannah Green, and Eric Bonneil, and Graca Raposo, and Pierre Thibault, and Roland Le Borgne, and Jean-Paul Vincent
Division of Developmental Biology, MRC National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK. kbecket@nimr.mrc.ac.uk

Wingless acts as a morphogen in Drosophila wing discs, where it specifies cell fates and controls growth several cell diameters away from its site of expression. Thus, despite being acylated and membrane associated, Wingless spreads in the extracellular space. Recent studies have focussed on identifying the route that Wingless follows in the secretory pathway and determining how it is packaged for release. We have found that, in medium conditioned by Wingless-expressing Drosophila S2 cells, Wingless is present on exosome-like vesicles and that this fraction activates signal transduction. Proteomic analysis shows that Wingless-containing exosome-like structures contain many Drosophila proteins that are homologous to mammalian exosome proteins. In addition, Evi, a multipass transmembrane protein, is also present on exosome-like vesicles. Using these exosome markers and a cell-based RNAi assay, we found that the small GTPase Rab11 contributes significantly to exosome production. This finding allows us to conclude from in vivo Rab11 knockdown experiments, that exosomes are unlikely to contribute to Wingless secretion and gradient formation in wing discs. Consistent with this conclusion, extracellularly tagged Evi expressed from a Bacterial Artificial Chromosome is not released from imaginal disc Wingless-expressing cells.

UI MeSH Term Description Entries
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004330 Drosophila A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology. Fruit Fly, Drosophila,Drosophila Fruit Flies,Drosophila Fruit Fly,Drosophilas,Flies, Drosophila Fruit,Fly, Drosophila Fruit,Fruit Flies, Drosophila
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D047908 Intracellular Signaling Peptides and Proteins Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors. Intracellular Signaling Peptides,Intracellular Signaling Proteins,Peptides, Intracellular Signaling,Proteins, Intracellular Signaling,Signaling Peptides, Intracellular,Signaling Proteins, Intracellular
D051155 Wnt1 Protein A proto-oncogene protein and member of the Wnt family of proteins. It is expressed in the caudal MIDBRAIN and is essential for proper development of the entire mid-/hindbrain region. Proto-Oncogene Protein Int-1,Proto-Oncogene Protein Wnt-1,Wnt1 Proto-Oncogene Protein,Wnt-1 Protein,c-int Protein,Int-1, Proto-Oncogene Protein,Proto Oncogene Protein Int 1,Proto Oncogene Protein Wnt 1,Proto-Oncogene Protein, Wnt1,Wnt 1 Protein,Wnt-1, Proto-Oncogene Protein,Wnt1 Proto Oncogene Protein
D055354 Exosomes A type of extracellular vesicle, containing RNA and proteins, that is secreted into the extracellular space by EXOCYTOSIS when MULTIVESICULAR BODIES fuse with the PLASMA MEMBRANE.
D060227 Imaginal Discs Hollow sacs of cells in LARVA that form adult structures in insects during BIOLOGICAL METAMORPHOSIS. Imaginal Disks,Disc, Imaginal,Discs, Imaginal,Disk, Imaginal,Disks, Imaginal,Imaginal Disc,Imaginal Disk
D020691 rab GTP-Binding Proteins A large family of MONOMERIC GTP-BINDING PROTEINS that play a key role in cellular secretory and endocytic pathways. Rab GTPase,rab G-Proteins,rab GTP-Binding Protein,rab GTPases,G-Proteins, rab,GTP-Binding Protein, rab,GTP-Binding Proteins, rab,GTPase, Rab,GTPases, rab,Protein, rab GTP-Binding,rab G Proteins,rab GTP Binding Protein,rab GTP Binding Proteins
D022142 Secretory Vesicles Vesicles derived from the GOLGI APPARATUS containing material to be released at the cell surface. SLMVs,Secretory Granules,Synaptic Like Microvesicles,Synaptic-Like Microvesicles,Zymogen Granules,Condensing Vacuoles,Condensing Vacuole,Granule, Secretory,Granule, Zymogen,Microvesicle, Synaptic-Like,Secretory Granule,Secretory Vesicle,Synaptic Like Microvesicle,Synaptic-Like Microvesicle,Vacuole, Condensing,Vesicle, Secretory,Zymogen Granule
D022202 Chromosomes, Artificial, Bacterial DNA constructs that are composed of, at least, a REPLICATION ORIGIN, for successful replication, propagation to and maintenance as an extra chromosome in bacteria. In addition, they can carry large amounts (about 200 kilobases) of other sequence for a variety of bioengineering purposes. Artificial Chromosomes, Bacterial,Bacterial Artificial Chromosomes,BAC (Chromosome),BACs (Chromosomes),Chromosomes, Bacterial Artificial,Artificial Chromosome, Bacterial,Bacterial Artificial Chromosome,Chromosome, Bacterial Artificial

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