PXD014559 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Tetraspanin-6 antagonizes the release of exosomes by stimulating the lysosomal degradation of syntenin and syndecan-4 |
Description | Exosomes, 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. |
HostingRepository | PRIDE |
AnnounceDate | 2020-02-12 |
AnnouncementXML | Submission_2020-02-12_06:20:27.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | AUDEBERT Stephane |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-07-10 05:50:38 | ID requested | |
⏵ 1 | 2020-02-12 06:20:28 | announced | |
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 affiliation | Marseille 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 email | Jean-Paul.Borg@inserm.fr |
lab head | |
AUDEBERT Stephane |
contact affiliation | Pharmacology department |
contact email | stephane.audebert@inserm.fr |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD014559
- Label: PRIDE project
- Name: Tetraspanin-6 antagonizes the release of exosomes by stimulating the lysosomal degradation of syntenin and syndecan-4