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PXD014559-1

PXD014559 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTetraspanin-6 antagonizes the release of exosomes by stimulating the lysosomal degradation of syntenin and syndecan-4
DescriptionExosomes, extracellular vesicles (EV) of endosomal origin, emerge as master regulators of cell-to-cell signaling in physiology and various systemic diseases. Exosomes are highly enriched in tetraspanins (TSPN) and syndecans (SDC), the latter occurring mainly in proteolytically-cleaved form, as membrane-spanning C-terminal fragments of the proteins. While both protein families are membrane scaffolds appreciated for their role in exosome formation, composition and activity, we currently ignore whether these work together to control exosome biology. Here we show that TSPN6, a poorly characterized tetraspanin, acts as a negative regulator of exosome release by supporting the lysosomal degradation of SDC4 and syntenin. In addition, we demonstrate that TSPN6 tightly associates with SDC4. Interestingly, TSPN6-dependent lysosomal degradation of syntenin strictly requires SDC4. TSPN6 also inhibits the shedding of the SDC4-ectodomain, mimicking the effects of matrix metalloproteinase inhibitors. Taken together our data identify TSPN6 as a regulator of the trafficking and processing of SDC4 and highlight an important physical and functional interconnection between these membrane scaffolds for the production of exosomes. These findings clarify our understanding of the molecular determinants governing EV formation and have potentially broad impact for EV-related biomedicine.
HostingRepositoryPRIDE
AnnounceDate2020-02-12
AnnouncementXMLSubmission_2020-02-12_06:20:27.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAUDEBERT Stephane
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-07-10 05:50:38ID requested
12020-02-12 06:20:28announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Human, exosomes, Tetraspanin, syntenin, LC-MSMS, GFP-Trap
Contact List
Jean-Paul BORG
contact affiliationMarseille Proteomique Centre de Recherche en Cancérologie de Marseille, CRCM Inserm UMR1068, CNRS UMR7258, Aix Marseille Université U105, Institut Paoli Calmettes 27 Boulevard Leï Roure CS30059 13273 Marseille Cedex 09 France
contact emailJean-Paul.Borg@inserm.fr
lab head
AUDEBERT Stephane
contact affiliationPharmacology department
contact emailstephane.audebert@inserm.fr
dataset submitter
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