Abstract
The biogenesis of exosomes, small secreted vesicles involved in signalling processes, remains incompletely understood. Here, we report evidence that the syndecan heparan sulphate proteoglycans and their cytoplasmic adaptor syntenin control the formation of exosomes. Syntenin interacts directly with ALIX through LYPX(n)L motifs, similarly to retroviral proteins, and supports the intraluminal budding of endosomal membranes. Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs, and impact on the trafficking and confinement of FGF signals. This study identifies a key role for syndecan-syntenin-ALIX in membrane transport and signalling processes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cell Line, Tumor
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Endosomal Sorting Complexes Required for Transport / genetics
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Endosomal Sorting Complexes Required for Transport / metabolism*
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Exosomes / metabolism*
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Fibroblast Growth Factors / metabolism
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Heparitin Sulfate / metabolism
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Humans
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Mice
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Protein Interaction Domains and Motifs
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Protein Transport
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RNA Interference
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Receptors, Fibroblast Growth Factor / metabolism
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Recombinant Fusion Proteins / metabolism
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Signal Transduction*
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Syndecans / genetics
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Syndecans / metabolism*
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Syntenins / genetics
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Syntenins / metabolism*
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Time Factors
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Transfection
Substances
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Calcium-Binding Proteins
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Cell Cycle Proteins
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Endosomal Sorting Complexes Required for Transport
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PDCD6IP protein, human
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Pdcd6ip protein, mouse
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Receptors, Fibroblast Growth Factor
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Recombinant Fusion Proteins
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Syndecans
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Syntenins
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Fibroblast Growth Factors
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Heparitin Sulfate