Author:

Keywords:

exosome, heparan-sulfate proteoglycans, multi-vesicular body, syndecan, ALIX, syntenin, pdz protein, ESCRT, Science & Technology, Life Sciences & Biomedicine, Cell Biology, MULTIVESICULAR BODY BIOGENESIS, HEPARAN-SULFATE PROTEOGLYCANS, ESCRT MACHINERY, PLASMA-MEMBRANE, DOMAIN BINDING, CELL-ADHESION, PDZ PROTEIN, MECHANISM, ENDOSOMES, VESICLES, Animals, Binding Sites, Calcium-Binding Proteins, Cell Cycle Proteins, Cell Line, Tumor, Endosomal Sorting Complexes Required for Transport, Exosomes, Fibroblast Growth Factors, Heparitin Sulfate, Humans, Mice, Protein Interaction Domains and Motifs, Protein Transport, RNA Interference, Receptors, Fibroblast Growth Factor, Recombinant Fusion Proteins, Signal Transduction, Syndecans, Syntenins, Time Factors, Transfection, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology, 3101 Biochemistry and cell biology

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.